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1. Adoptive transfer of personalized neoantigen-reactive TCR-transduced T cells in metastatic colorectal cancer: phase 2 trial interim results

Author

Parkhurst, Maria, Goff, Stephanie L., Lowery, Frank J., Beyer, Rachel K., Halas, Hyunmi, Robbins, Paul F., Prickett, Todd D., Gartner, Jared J., Sindiri, Sivasish, Krishna, Sri, Zacharakis, Nikolaos, Ngo, Lien, Ray, Satyajit, Bera, Alakesh, Shepherd, Ryan, Levin, Noam, Kim, Sanghyun P., Copeland, Amy, Nah, Shirley, Levi, Shoshana, Parikh, Neilesh, Kwong, Mei Li M., Klemen, Nicholas D., Yang, James C., and Rosenberg, Steven A.

Published
2024
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2. Internal checkpoint regulates T cell neoantigen reactivity and susceptibility to PD1 blockade

Author

Palmer, Douglas C., Webber, Beau R., Patel, Yogin, Johnson, Matthew J., Kariya, Christine M., Lahr, Walker S., Parkhurst, Maria R., Gartner, Jared J., Prickett, Todd D., Lowery, Frank J., Kishton, Rigel J., Gurusamy, Devikala, Franco, Zulmarie, Vodnala, Suman K., Diers, Miechaleen D., Wolf, Natalie K., Slipek, Nicholas J., McKenna, David H., Sumstad, Darin, Viney, Lydia, Henley, Tom, Bürckstümmer, Tilmann, Baker, Oliver, Hu, Ying, Yan, Chunhua, Meerzaman, Daoud, Padhan, Kartik, Lo, Winnie, Malekzadeh, Parisa, Jia, Li, Deniger, Drew C., Patel, Shashank J., Robbins, Paul F., McIvor, R. Scott, Choudhry, Modassir, Rosenberg, Steven A., Moriarity, Branden S., and Restifo, Nicholas P.

Published
2022
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3. mRNA vaccine-induced neoantigen-specific T cell immunity in patients with gastrointestinal cancer

Author

Cafri, Gal, Gartner, Jared J., Zaks, Tal, Hopson, Kristen, Levin, Noam, Paria, Biman C., Parkhurst, Maria R., Yossef, Rami, Lowery, Frank J., Jafferji, Mohammad S., Prickett, Todd D., Goff, Stephanie L., McGowan, Christine T., Seitter, Samantha, Shindorf, Mackenzie L., Parikh, Anup, Chatani, Praveen D., Robbins, Paul F., and Rosenberg, Steven A.

Subjects
Gene mutations -- Research, Immunological research, T cells -- Genetic aspects -- Health aspects, Immune response -- Genetic aspects -- Health aspects, Gastrointestinal cancer -- Genetic aspects -- Care and treatment, Immunotherapy -- Methods, Messenger RNA -- Health aspects, Cancer vaccines -- Usage, Tumor antigens -- Health aspects, Health care industry
Abstract

BACKGROUND. Therapeutic vaccinations against cancer have mainly targeted differentiation antigens, cancer-testis antigens, and overexpressed antigens and have thus far resulted in little clinical benefit. Studies conducted by multiple groups have demonstrated that T cells recognizing neoantigens are present in most cancers and offer a specific and highly immunogenic target for personalized vaccination. METHODS. We recently developed a process using tumor-infiltrating lymphocytes to identify the specific immunogenic mutations expressed in patients' tumors. Here, validated, defined neoantigens, predicted neoepitopes, and mutations of driver genes were concatenated into a single mRNA construct to vaccinate patients with metastatic gastrointestinal cancer. RESULTS. The vaccine was safe and elicited mutation-specific T cell responses against predicted neoepitopes not detected before vaccination. Furthermore, we were able to isolate and verify T cell receptors targeting [KRAS.sup.G12D] mutation. We observed no objective clinical responses in the 4 patients treated in this trial. CONCLUSION. This vaccine was safe, and potential future combination of such vaccines with checkpoint inhibitors or adoptive T cell therapy should be evaluated for possible clinical benefit in patients with common epithelial cancers. TRIAL REGISTRATION. Phase I/II protocol (NCT03480152) was approved by the IRB committee of the NIH and the FDA. FUNDING. Center for Clinical Research, NCI, NIH., Introduction Protective vaccination against infectious diseases has proven to be one of the most effective health measures in medicine; however, therapeutic vaccination against established diseases such as persistent infections and [...]

Published
2020
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4. Cell surface marker-based capture of neoantigen-reactive CD8+T-cell receptors from metastatic tumor digests

Author

Chatani, Praveen D, primary, Lowery, Frank J, additional, Parikh, Neilesh B, additional, Hitscherich, Kyle J, additional, Yossef, Rami, additional, Hill, Victoria, additional, Gartner, Jared J, additional, Paria, Biman, additional, Florentin, Maria, additional, Ray, Satyajit, additional, Bera, Alakesh, additional, Parkhust, Maria, additional, Robbins, Paul, additional, Krishna, Sri, additional, and Rosenberg, Steven A, additional

Published
2023
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5. Supplementary Data from Adoptive Cellular Therapy with Autologous Tumor-Infiltrating Lymphocytes and T-cell Receptor–Engineered T Cells Targeting Common p53 Neoantigens in Human Solid Tumors

Author

Kim, Sanghyun P., primary, Vale, Nolan R., primary, Zacharakis, Nikolaos, primary, Krishna, Sri, primary, Yu, Zhiya, primary, Gasmi, Billel, primary, Gartner, Jared J., primary, Sindiri, Sivasish, primary, Malekzadeh, Parisa, primary, Deniger, Drew C., primary, Lowery, Frank J., primary, Parkhurst, Maria R., primary, Ngo, Lien T., primary, Ray, Satyajit, primary, Li, Yong F., primary, Hill, Victoria, primary, Florentin, Maria, primary, Masi, Robert V., primary, Paria, Biman C., primary, Levin, Noam, primary, Bera, Alakesh, primary, Hedges, Elizabeth A., primary, Choi, Agnes, primary, Chatani, Praveen D., primary, Parikh, Anup Y., primary, Levi, Shoshana, primary, Seitter, Samantha, primary, Lu, Yong-Chen, primary, Zheng, Zhili, primary, Prickett, Todd D., primary, Jia, Li, primary, Hernandez, Jonathan M., primary, Hoang, Chuong D., primary, Robbins, Paul F., primary, Goff, Stephanie L., primary, Sherry, Richard M., primary, Yang, James C., primary, and Rosenberg, Steven A., primary

Published
2023
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6. Supplementary Figure from Adoptive Cellular Therapy with Autologous Tumor-Infiltrating Lymphocytes and T-cell Receptor–Engineered T Cells Targeting Common p53 Neoantigens in Human Solid Tumors

Author

Kim, Sanghyun P., primary, Vale, Nolan R., primary, Zacharakis, Nikolaos, primary, Krishna, Sri, primary, Yu, Zhiya, primary, Gasmi, Billel, primary, Gartner, Jared J., primary, Sindiri, Sivasish, primary, Malekzadeh, Parisa, primary, Deniger, Drew C., primary, Lowery, Frank J., primary, Parkhurst, Maria R., primary, Ngo, Lien T., primary, Ray, Satyajit, primary, Li, Yong F., primary, Hill, Victoria, primary, Florentin, Maria, primary, Masi, Robert V., primary, Paria, Biman C., primary, Levin, Noam, primary, Bera, Alakesh, primary, Hedges, Elizabeth A., primary, Choi, Agnes, primary, Chatani, Praveen D., primary, Parikh, Anup Y., primary, Levi, Shoshana, primary, Seitter, Samantha, primary, Lu, Yong-Chen, primary, Zheng, Zhili, primary, Prickett, Todd D., primary, Jia, Li, primary, Hernandez, Jonathan M., primary, Hoang, Chuong D., primary, Robbins, Paul F., primary, Goff, Stephanie L., primary, Sherry, Richard M., primary, Yang, James C., primary, and Rosenberg, Steven A., primary

Published
2023
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7. Data from Adoptive Cellular Therapy with Autologous Tumor-Infiltrating Lymphocytes and T-cell Receptor–Engineered T Cells Targeting Common p53 Neoantigens in Human Solid Tumors

Author

Kim, Sanghyun P., primary, Vale, Nolan R., primary, Zacharakis, Nikolaos, primary, Krishna, Sri, primary, Yu, Zhiya, primary, Gasmi, Billel, primary, Gartner, Jared J., primary, Sindiri, Sivasish, primary, Malekzadeh, Parisa, primary, Deniger, Drew C., primary, Lowery, Frank J., primary, Parkhurst, Maria R., primary, Ngo, Lien T., primary, Ray, Satyajit, primary, Li, Yong F., primary, Hill, Victoria, primary, Florentin, Maria, primary, Masi, Robert V., primary, Paria, Biman C., primary, Levin, Noam, primary, Bera, Alakesh, primary, Hedges, Elizabeth A., primary, Choi, Agnes, primary, Chatani, Praveen D., primary, Parikh, Anup Y., primary, Levi, Shoshana, primary, Seitter, Samantha, primary, Lu, Yong-Chen, primary, Zheng, Zhili, primary, Prickett, Todd D., primary, Jia, Li, primary, Hernandez, Jonathan M., primary, Hoang, Chuong D., primary, Robbins, Paul F., primary, Goff, Stephanie L., primary, Sherry, Richard M., primary, Yang, James C., primary, and Rosenberg, Steven A., primary

Published
2023
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8. Supplementary Data from Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers

Author

Parkhurst, Maria R., primary, Robbins, Paul F., primary, Tran, Eric, primary, Prickett, Todd D., primary, Gartner, Jared J., primary, Jia, Li, primary, Ivey, Gabriel, primary, Li, Yong F., primary, El-Gamil, Mona, primary, Lalani, Almin, primary, Crystal, Jessica S., primary, Sachs, Abraham, primary, Groh, Eric, primary, Ray, Satyajit, primary, Ngo, Lien T., primary, Kivitz, Scott, primary, Pasetto, Anna, primary, Yossef, Rami, primary, Lowery, Frank J., primary, Goff, Stephanie L., primary, Lo, Winifred, primary, Cafri, Gal, primary, Deniger, Drew C., primary, Malekzadeh, Parisa, primary, Ahmadzadeh, Mojgan, primary, Wunderlich, John R., primary, Somerville, Robert P.T., primary, and Rosenberg, Steven A., primary

Published
2023
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9. Data from Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers

Author

Parkhurst, Maria R., primary, Robbins, Paul F., primary, Tran, Eric, primary, Prickett, Todd D., primary, Gartner, Jared J., primary, Jia, Li, primary, Ivey, Gabriel, primary, Li, Yong F., primary, El-Gamil, Mona, primary, Lalani, Almin, primary, Crystal, Jessica S., primary, Sachs, Abraham, primary, Groh, Eric, primary, Ray, Satyajit, primary, Ngo, Lien T., primary, Kivitz, Scott, primary, Pasetto, Anna, primary, Yossef, Rami, primary, Lowery, Frank J., primary, Goff, Stephanie L., primary, Lo, Winifred, primary, Cafri, Gal, primary, Deniger, Drew C., primary, Malekzadeh, Parisa, primary, Ahmadzadeh, Mojgan, primary, Wunderlich, John R., primary, Somerville, Robert P.T., primary, and Rosenberg, Steven A., primary

Published
2023
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10. Supplementary Figures from Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers

Author

Parkhurst, Maria R., primary, Robbins, Paul F., primary, Tran, Eric, primary, Prickett, Todd D., primary, Gartner, Jared J., primary, Jia, Li, primary, Ivey, Gabriel, primary, Li, Yong F., primary, El-Gamil, Mona, primary, Lalani, Almin, primary, Crystal, Jessica S., primary, Sachs, Abraham, primary, Groh, Eric, primary, Ray, Satyajit, primary, Ngo, Lien T., primary, Kivitz, Scott, primary, Pasetto, Anna, primary, Yossef, Rami, primary, Lowery, Frank J., primary, Goff, Stephanie L., primary, Lo, Winifred, primary, Cafri, Gal, primary, Deniger, Drew C., primary, Malekzadeh, Parisa, primary, Ahmadzadeh, Mojgan, primary, Wunderlich, John R., primary, Somerville, Robert P.T., primary, and Rosenberg, Steven A., primary

Published
2023
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11. Astrocyte-induced Cdk5 expedites breast cancer brain metastasis by suppressing MHC-I expression to evade immune recognition

Author

Yuzhalin, Arseniy E., Lowery, Frank J., Saito, Yohei, Yuan, Xiangliang, Yao, Jun, Duan, Yimin, Ding, Jingzhen, Acharya, Sunil, Zhang, Chenyu, Fajardo, Abigail, Chen, Hao-Nien, Wei, Yongkun, Sun, Yutong, Zhang, Lin, Xiao, Yi, Li, Ping, Lorenzi, Philip L., Huse, Jason T., Fan, Huihui, Zhao, Zhongming, Hung, Mien-Chie, and Yu, Dihua

Abstract

Brain metastases (BrMs) evade the immune response to develop in the brain, yet the mechanisms of BrM immune evasion remains unclear. This study shows that brain astrocytes induce the overexpression of neuronal-specific cyclin-dependent kinase 5 (Cdk5) in breast cancer-derived BrMs, which facilitates BrM outgrowth in mice. Cdk5-overexpressing BrMs exhibit reduced expression and function of the class I major histocompatibility complex (MHC-I) and antigen-presentation pathway, which are restored by inhibiting Cdk5 genetically or pharmacologically, as evidenced by single-cell RNA sequencing and functional studies. Mechanistically, Cdk5 suppresses MHC-I expression on the cancer cell membrane through the Irf2bp1–Stat1–importin α–Nlrc5 pathway, enabling BrMs to avoid recognition by T cells. Treatment with roscovitine—a clinically applicable Cdk5 inhibitor—alone or combined with immune checkpoint inhibitors, significantly reduces BrM burden and increases tumour-infiltrating functional CD8+lymphocytes in mice. Thus, astrocyte-induced Cdk5 overexpression endorses BrM immune evasion, whereas therapeutically targeting Cdk5 markedly improves the efficacy of immune checkpoint inhibitors and inhibits BrM growth.

Published
2024
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13. Phenotypic signatures of circulating neoantigen-reactive CD8+ T cells in patients with metastatic cancers

Author

Yossef, Rami, Krishna, Sri, Sindiri, Sivasish, Lowery, Frank J., Copeland, Amy R., Gartner, Jared J., Parkhurst, Maria R., Parikh, Neilesh B., Hitscherich, Kyle J., Levi, Shoshana T., Chatani, Praveen D., Zacharakis, Nikolaos, Levin, Noam, Vale, Nolan R., Nah, Shirley K., Dinerman, Aaron, Hill, Victoria K., Ray, Satyajit, Bera, Alakesh, Levy, Lior, Jia, Li, Kelly, Michael C., Goff, Stephanie L., Robbins, Paul F., and Rosenberg, Steven A.

Published
2023
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18. Supplementary Data from Antigen Experienced T Cells from Peripheral Blood Recognize p53 Neoantigens

Author

Malekzadeh, Parisa, primary, Yossef, Rami, primary, Cafri, Gal, primary, Paria, Biman C., primary, Lowery, Frank J., primary, Jafferji, Mohammad, primary, Good, Meghan L., primary, Sachs, Abraham, primary, Copeland, Amy R., primary, Kim, Sanghyun P., primary, Kivitz, Scott, primary, Parkhurst, Maria R., primary, Robbins, Paul F., primary, Ray, Satyajit, primary, Xi, Liqiang, primary, Raffeld, Mark, primary, Yu, Zhiya, primary, Restifo, Nicholas P., primary, Somerville, Robert P.T., primary, Rosenberg, Steven A., primary, and Deniger, Drew C., primary

Published
2023
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23. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth

Author

Zhang, Lin, Zhang, Siyuan, Yao, Jun, Lowery, Frank J., Zhang, Qingling, Huang, Wen-Chien, Li, Ping, Li, Min, Wang, Xiao, Zhang, Chenyu, Wang, Hai, Ellis, Kenneth, Cheerathodi, Mujeeburahiman, McCarty, Joseph H., Palmieri, Diane, Saunus, Jodi, Lakhani, Sunil, Huang, Suyun, Sahin, Aysegul A., Aldape, Kenneth D., Steeg, Patricia S., and Yu, Dihua

Subjects
Gene mutations -- Identification and classification -- Health aspects, Gene expression -- Health aspects, Metastasis -- Genetic aspects, Disease susceptibility -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The development of life-threatening cancer metastases at distant organs requires disseminated tumour cells' adaptation to, and co-evolution with, the drastically different microenvironments of metastatic sites (1). Cancer cells of common [...]

Published
2015

24. Adoptive Cellular Therapy with Autologous Tumor-Infiltrating Lymphocytes and T-cell Receptor–Engineered T Cells Targeting Common p53 Neoantigens in Human Solid Tumors

Author

Kim, Sanghyun P., primary, Vale, Nolan R., additional, Zacharakis, Nikolaos, additional, Krishna, Sri, additional, Yu, Zhiya, additional, Gasmi, Billel, additional, Gartner, Jared J., additional, Sindiri, Sivasish, additional, Malekzadeh, Parisa, additional, Deniger, Drew C., additional, Lowery, Frank J., additional, Parkhurst, Maria R., additional, Ngo, Lien T., additional, Ray, Satyajit, additional, Li, Yong F., additional, Hill, Victoria, additional, Florentin, Maria, additional, Masi, Robert V., additional, Paria, Biman C., additional, Levin, Noam, additional, Bera, Alakesh, additional, Hedges, Elizabeth A., additional, Choi, Agnes, additional, Chatani, Praveen D., additional, Parikh, Anup Y., additional, Levi, Shoshana, additional, Seitter, Samantha, additional, Lu, Yong-Chen, additional, Zheng, Zhili, additional, Prickett, Todd D., additional, Jia, Li, additional, Hernandez, Jonathan M., additional, Hoang, Chuong D., additional, Robbins, Paul F., additional, Goff, Stephanie L., additional, Sherry, Richard M., additional, Yang, James C., additional, and Rosenberg, Steven A., additional

Published
2022
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27. A phenotypic signature that identifies neoantigen-reactive T cells in fresh human lung cancers

Author

Hanada, Ken-ichi, primary, Zhao, Chihao, additional, Gil-Hoyos, Raul, additional, Gartner, Jared J., additional, Chow-Parmer, Christopher, additional, Lowery, Frank J., additional, Krishna, Sri, additional, Prickett, Todd D., additional, Kivitz, Scott, additional, Parkhurst, Maria R., additional, Wong, Nathan, additional, Rae, Zachary, additional, Kelly, Michael C., additional, Goff, Stephanie L., additional, Robbins, Paul F., additional, Rosenberg, Steven A., additional, and Yang, James C., additional

Published
2022
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28. Molecular signatures of antitumor neoantigen-reactive T cells from metastatic human cancers

Author

Lowery, Frank J., primary, Krishna, Sri, additional, Yossef, Rami, additional, Parikh, Neilesh B., additional, Chatani, Praveen D., additional, Zacharakis, Nikolaos, additional, Parkhurst, Maria R., additional, Levin, Noam, additional, Sindiri, Sivasish, additional, Sachs, Abraham, additional, Hitscherich, Kyle J., additional, Yu, Zhiya, additional, Vale, Nolan R., additional, Lu, Yong-Chen, additional, Zheng, Zhili, additional, Jia, Li, additional, Gartner, Jared J., additional, Hill, Victoria K., additional, Copeland, Amy R., additional, Nah, Shirley K., additional, Masi, Robert V., additional, Gasmi, Billel, additional, Kivitz, Scott, additional, Paria, Biman C., additional, Florentin, Maria, additional, Kim, Sanghyun P., additional, Hanada, Ken-ichi, additional, Li, Yong F., additional, Ngo, Lien T., additional, Ray, Satyajit, additional, Shindorf, Mackenzie L., additional, Levi, Shoshana T., additional, Shepherd, Ryan, additional, Toy, Chris, additional, Parikh, Anup Y., additional, Prickett, Todd D., additional, Kelly, Michael C., additional, Beyer, Rachel, additional, Goff, Stephanie L., additional, Yang, James C., additional, Robbins, Paul F., additional, and Rosenberg, Steven A., additional

Published
2022
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30. Abstract 127: Single cell mapping of tumor infiltrating lymphocytes enables neoantigen-reactive T cell identification in metastatic human cancer

Author

Lowery, Frank J., primary, Krishna, Sri, additional, Yossef, Rami, additional, Chatani, Praveen D., additional, Parikh, Neilesh B., additional, Lu, Yong-Chen, additional, Zacharakis, Nikolaos, additional, Levin, Noam, additional, Hanada, Ken-ichi, additional, Yang, James C., additional, Robbins, Paul F., additional, Parkhurst, Maria R., additional, and Rosenberg, Steven A., additional

Published
2021
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32. Identification and Validation of T-cell Receptors Targeting RAS Hotspot Mutations in Human Cancers for Use in Cell-based Immunotherapy

Author

Levin, Noam, primary, Paria, Biman C., additional, Vale, Nolan R., additional, Yossef, Rami, additional, Lowery, Frank J., additional, Parkhurst, Maria R., additional, Yu, Zhiya, additional, Florentin, Maria, additional, Cafri, Gal, additional, Gartner, Jared J., additional, Shindorf, Mackenzie L., additional, Ngo, Lien T., additional, Ray, Satyajit, additional, Kim, Sanghyun P., additional, Copeland, Amy R., additional, Robbins, Paul F., additional, and Rosenberg, Steven A., additional

Published
2021
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33. Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer

Author

Krishna, Sri, primary, Lowery, Frank J., additional, Copeland, Amy R., additional, Bahadiroglu, Erol, additional, Mukherjee, Ratnadeep, additional, Jia, Li, additional, Anibal, James T., additional, Sachs, Abraham, additional, Adebola, Serifat O., additional, Gurusamy, Devikala, additional, Yu, Zhiya, additional, Hill, Victoria, additional, Gartner, Jared J., additional, Li, Yong F., additional, Parkhurst, Maria, additional, Paria, Biman, additional, Kvistborg, Pia, additional, Kelly, Michael C., additional, Goff, Stephanie L., additional, Altan-Bonnet, Grégoire, additional, Robbins, Paul F., additional, and Rosenberg, Steven A., additional

Published
2020
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34. Rapid Identification and Evaluation of Neoantigen-reactive T-Cell Receptors From Single Cells

Author

Paria, Biman C., primary, Levin, Noam, additional, Lowery, Frank J., additional, Pasetto, Anna, additional, Deniger, Drew C., additional, Parkhurst, Maria R., additional, Yossef, Rami, additional, Kim, Sanghyun P., additional, Florentin, Maria, additional, Ngo, Lien T., additional, Ray, Satyajit, additional, Krishna, Sri, additional, Robbins, Paul F., additional, and Rosenberg, Steven A., additional

Published
2020
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35. Internal checkpoint regulates T cell neoantigen reactivity and susceptibility to PD1 blockade

Author

Palmer, Douglas C., primary, Webber, Beau R., additional, Patel, Yogin, additional, Johnson, Matthew J., additional, Kariya, Christine M., additional, Lahr, Walker S., additional, Parkhurst, Maria R., additional, Gartner, Jared J, additional, Prickett, Todd D, additional, Lowery, Frank J., additional, Kishton, Rigel J., additional, Gurusamy, Devikala, additional, Franco, Zulmarie, additional, Vodnala, Suman K., additional, Diers, Miechaleen D., additional, Wolf, Natalie K., additional, Slipek, Nicholas J., additional, McKenna, David H., additional, Sumstad, Darin, additional, Viney, Lydia, additional, Henley, Tom, additional, Bürckstümmer, Tilmann, additional, Baker, Oliver, additional, Hu, Ying, additional, Yan, Chunhua, additional, Meerzaman, Daoud, additional, Padhan, Kartik, additional, Lo, Winnie, additional, Malekzadeh, Parisa, additional, Jia, Li, additional, Deniger, Drew C., additional, Patel, Shashank J., additional, Robbins, Paul F., additional, McIvor, R. Scott, additional, Choudhry, Modassir, additional, Rosenberg, Steven A., additional, Moriarity, Branden S., additional, and Restifo, Nicholas P., additional

Published
2020
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36. Antigen Experienced T Cells from Peripheral Blood Recognize p53 Neoantigens

Author

Malekzadeh, Parisa, primary, Yossef, Rami, additional, Cafri, Gal, additional, Paria, Biman C., additional, Lowery, Frank J., additional, Jafferji, Mohammad, additional, Good, Meghan L., additional, Sachs, Abraham, additional, Copeland, Amy R., additional, Kim, Sanghyun P., additional, Kivitz, Scott, additional, Parkhurst, Maria R., additional, Robbins, Paul F., additional, Ray, Satyajit, additional, Xi, Liqiang, additional, Raffeld, Mark, additional, Yu, Zhiya, additional, Restifo, Nicholas P., additional, Somerville, Robert P.T., additional, Rosenberg, Steven A., additional, and Deniger, Drew C., additional

Published
2020
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38. Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers

Author

Parkhurst, Maria R., primary, Robbins, Paul F., additional, Tran, Eric, additional, Prickett, Todd D., additional, Gartner, Jared J., additional, Jia, Li, additional, Ivey, Gabriel, additional, Li, Yong F., additional, El-Gamil, Mona, additional, Lalani, Almin, additional, Crystal, Jessica S., additional, Sachs, Abraham, additional, Groh, Eric, additional, Ray, Satyajit, additional, Ngo, Lien T., additional, Kivitz, Scott, additional, Pasetto, Anna, additional, Yossef, Rami, additional, Lowery, Frank J., additional, Goff, Stephanie L., additional, Lo, Winifred, additional, Cafri, Gal, additional, Deniger, Drew C., additional, Malekzadeh, Parisa, additional, Ahmadzadeh, Mojgan, additional, Wunderlich, John R., additional, Somerville, Robert P.T., additional, and Rosenberg, Steven A., additional

Published
2019
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39. High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

Author

Detterbeck Frank, Gettinger Scott, Boffa Daniel, Tanoue Lynn, Frangia Konstantina, Panagopoulos Nikolaos, Liceaga Camil, Gopinath Arun, Tzelepi Vassiliki, Zolota Vassiliki, Lowery Frank J, Anagnostou Valsamo K, Homer Robert J, Dougenis Dimitrios, Rimm David L, and Syrigos Konstantinos N

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results. Methods Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA®, a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome. Results Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005). Conclusions Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients.

Published
2010
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41. Quantitative evaluation of protein expression as a function of tissue microarray core diameter: is a large (1.5 mm) core better than a small (0.6 mm) core?

Author

Anagnostou, Valsamo K., Lowery, Frank J., Syrigos, Konstantinos N., Cagle, Philip T., and Rimm, David L.

Subjects
Cellular proteins -- Health aspects -- Research, Growth factor receptors -- Health aspects -- Research, Biological markers -- Research, Tissue microarrays -- Usage, Health
Abstract

* Context.--Tissue microarrays (TMAs) have emerged as a high-throughput technology for protein evaluation in large cohorts. This technique allows maximization of tissue resources by analysis of sections from 0.6-mm to 1.5-mm core 'biopsies' of standard formalin-fixed, paraffin-embedded tissue blocks and by the processing of hundreds of cases arrayed on a single recipient block in an identical manner. Objective.--To assess the expression of a series of biomarkers as a function of core size. Although pathologists frequently feel better if larger core sizes are used, there is no evidence in the literature showing that large cores are better (or worse) than small cores for assessment of TMAs. Design.--Estrogen receptor, HER2/neu, epidermal growth factor receptor, STAT3, mTOR, and phospho-p70 S6 kinase were measured by immunofluorescence with automated quantitative analysis. One random 0.6-mm field (one 0.6-mm spot) was compared to 6 to 12 fields per spot, representing 1-mm and 1.5-mm cores, for 3 different tumor types. Results.--We show that measurement of a single random 0.6-mm spot was comparable to analysis of the whole 1mm or 1.5-mm spot (Pearson R coefficient varying from 0.87-0.98) for all markers tested. Conclusions.--Since TMA technology is now being used in all phases of biomarker development, this work shows that TMAs with 0.6-mm cores are as representative as those with any common larger core size for optimization of standardized experimental conditions. Given that a greater number of 0.6-cores can be arrayed in a single master block, use of this core size allows increased throughput and decreased cost. (Arch Pathol Lab Med. 2010;134:613-619), Tissue microarray (TMA) technology is a high-throughput research tool for assessing protein expression levels in large cohorts and allows for consecutive testing of multiple diagnostic and prognostic biomarkers. (1,2) Typically, [...]

Published
2010

44. Abstract 907: Brain microenvironment induced PTEN loss by microRNAs promotes brain metastasis

Author

Zhang, Lin, primary, Zhang, Siyaun, additional, Yao, Jun, additional, Lowery, Frank J. Lowery, additional, Zhang, Qingling, additional, Huang, Wen-Chien, additional, Li, Ping, additional, Li, Min, additional, Wang, Xiao, additional, Zhang, Chenyu, additional, Wang, Hai, additional, Ellis, Kenneth, additional, Cheerathodi, Mujeeburahiman, additional, McCarty, Joseph, additional, Palmieri, Diane, additional, Steeg, Patricia, additional, Saunus, Jodi S, additional, Lakhani, Sunil, additional, Huang, Suyun, additional, Sahin, Aysegul, additional, Aldape, Kenneth, additional, and Yu, Dihua, additional

Published
2016
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46. 14-3-3ζ Turns TGF-β’s Function from Tumor Suppressor to Metastasis Promoter in Breast Cancer by Contextual Changes of Smad Partners from p53 to Gli2

Author

Xu, Jia, primary, Acharya, Sunil, additional, Sahin, Ozgur, additional, Zhang, Qingling, additional, Saito, Yohei, additional, Yao, Jun, additional, Wang, Hai, additional, Li, Ping, additional, Zhang, Lin, additional, Lowery, Frank J., additional, Kuo, Wen-Ling, additional, Xiao, Yi, additional, Ensor, Joe, additional, Sahin, Aysegul A., additional, Zhang, Xiang H.-F., additional, Hung, Mien-Chie, additional, Zhang, Jitao David, additional, and Yu, Dihua, additional

Published
2015
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48. Inhibition of Type I Insulin-Like Growth Factor Receptor Signaling Attenuates the Development of Breast Cancer Brain Metastasis

Author

Saldana, Sandra M., primary, Lee, Heng-Huan, additional, Lowery, Frank J., additional, Khotskaya, Yekaterina B., additional, Xia, Weiya, additional, Zhang, Chenyu, additional, Chang, Shih-Shin, additional, Chou, Chao-Kai, additional, Steeg, Patricia S., additional, Yu, Dihua, additional, and Hung, Mien-Chie, additional

Published
2013
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50. High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

Author

Anagnostou, Valsamo K, primary, Lowery, Frank J, additional, Zolota, Vassiliki, additional, Tzelepi, Vassiliki, additional, Gopinath, Arun, additional, Liceaga, Camil, additional, Panagopoulos, Nikolaos, additional, Frangia, Konstantina, additional, Tanoue, Lynn, additional, Boffa, Daniel, additional, Gettinger, Scott, additional, Detterbeck, Frank, additional, Homer, Robert J, additional, Dougenis, Dimitrios, additional, Rimm, David L, additional, and Syrigos, Konstantinos N, additional

Published
2010
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