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39 results on '"Ray, Satyajit"'

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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8. The antigenic landscape of human influenza N2 neuraminidases from 2009 until 2017

Author

Catani, João Paulo Portela, primary, Smet, Anouk, additional, Ysenbaert, Tine, additional, Vuylsteke, Marnik, additional, Bottu, Guy, additional, Mathys, Janick, additional, Botzki, Alexander, additional, Cortes-Garcia, Guadalupe, additional, Strugnell, Tod, additional, Gomila, Raul, additional, Hamberger, John, additional, Catalan, John, additional, Ustyugova, Irina V, additional, Farrell, Timothy, additional, Stegalkina, Svetlana, additional, Ray, Satyajit, additional, LaRue, Lauren, additional, Saelens, Xavier, additional, and Vogel, Thorsten U, additional

Published
2024
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9. Author response: The antigenic landscape of human influenza N2 neuraminidases from 2009 until 2017

Author

Catani, João Paulo Portela, primary, Smet, Anouk, additional, Ysenbaert, Tine, additional, Vuylsteke, Marnik, additional, Bottu, Guy, additional, Mathys, Janick, additional, Botzki, Alexander, additional, Cortes-Garcia, Guadalupe, additional, Strugnell, Tod, additional, Gomila, Raul, additional, Hamberger, John, additional, Catalan, John, additional, Ustyugova, Irina V, additional, Farrell, Timothy, additional, Stegalkina, Svetlana, additional, Ray, Satyajit, additional, LaRue, Lauren, additional, Saelens, Xavier, additional, and Vogel, Thorsten U, additional

Published
2024
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11. Adoptive transfer of T lymphocytes retrovirally transduced to express personalized neoantigen reactive T cell receptors can mediate tumor regression in patients with metastatic colorectal cancer

Author

Parkhurst, Maria, primary, Goff, Stephanie, additional, Lowery, Frank, additional, Beyer, Rachel, additional, Halas, Hyunmi, additional, Robbins, Paul, additional, Gartner, Jared, additional, Sindiri, Sivasish, additional, Krishna, Sri, additional, Zacharakis, Nikolaos, additional, Ngo, Lien, additional, Ray, Satyajit, additional, Bera, Alakesh, additional, Shepherd, Ryan, additional, Levin, Noam, additional, Kim, Sanghyun, additional, Copeland, Amy, additional, Nah, Shirley, additional, Levi, Shoshana, additional, Parikh, Neilesh, additional, Kwong, Mei Li, additional, Klemen, Nicholas, additional, Yang, James, additional, and Rosenberg, Steven, additional

Published
2024
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14. The antigenic landscape of human influenza N2 neuraminidases from 2009 until 2017

Author

Portela Catani, João Paulo, primary, Smet, Anouk, additional, Ysenbaert, Tine, additional, Vuylsteke, Marnik, additional, Bottu, Guy, additional, Mathys, Janick, additional, Botzki, Alexander, additional, Cortes-Garcia, Guadalupe, additional, Strugnell, Tod, additional, Gomila, Raul, additional, Hamberger, John, additional, Catalan, John, additional, Ustyugova, Irina V., additional, Farrell, Timothy, additional, Stegalkina, Svetlana, additional, Ray, Satyajit, additional, LaRue, Lauren, additional, Saelens, Xavier, additional, and Vogel, Thorsten U., additional

Published
2023
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15. The antigenic landscape of human influenza N2 neuraminidases from 2009 until 2017

Author

Catani, Joao Paulo, primary, Smet, Anouk, additional, Ysenbaert, Tine, additional, Vuylsteke, Marnik, additional, Bottu, Guy, additional, Mathys, Janick, additional, Botzki, Alexander, additional, Cortes-Garcia, Guadalupe, additional, Strudnell, Tod, additional, Gomila, Raoul, additional, Hamberger, John, additional, Catalan, John, additional, Ustyugova, Irina, additional, Farrell, Timothy, additional, Stegalkina, Svetlana, additional, Ray, Satyajit, additional, LaRue, Lauren, additional, Saelens, Xavier, additional, and Vogel, Thorsten U, additional

Published
2023
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17. 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. 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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19. Supplementary Figures from Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer

Author

Lo, Winifred, primary, Parkhurst, Maria, primary, Robbins, Paul F., primary, Tran, Eric, primary, Lu, Yong-Chen, primary, Jia, Li, primary, Gartner, Jared J., primary, Pasetto, Anna, primary, Deniger, Drew, primary, Malekzadeh, Parisa, primary, Shelton, Thomas E., primary, Prickett, Todd, primary, Ray, Satyajit, primary, Kivitz, Scott, primary, Paria, Biman C., primary, Kriley, Isaac, primary, Schrump, David S., primary, and Rosenberg, Steven A., primary

Published
2023
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20. Supplementary Table 4 from Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer

Author

Lo, Winifred, primary, Parkhurst, Maria, primary, Robbins, Paul F., primary, Tran, Eric, primary, Lu, Yong-Chen, primary, Jia, Li, primary, Gartner, Jared J., primary, Pasetto, Anna, primary, Deniger, Drew, primary, Malekzadeh, Parisa, primary, Shelton, Thomas E., primary, Prickett, Todd, primary, Ray, Satyajit, primary, Kivitz, Scott, primary, Paria, Biman C., primary, Kriley, Isaac, primary, Schrump, David S., primary, and Rosenberg, Steven A., primary

Published
2023
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21. 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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22. 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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23. Supplementary Figure 5 from Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer

Author

Lo, Winifred, primary, Parkhurst, Maria, primary, Robbins, Paul F., primary, Tran, Eric, primary, Lu, Yong-Chen, primary, Jia, Li, primary, Gartner, Jared J., primary, Pasetto, Anna, primary, Deniger, Drew, primary, Malekzadeh, Parisa, primary, Shelton, Thomas E., primary, Prickett, Todd, primary, Ray, Satyajit, primary, Kivitz, Scott, primary, Paria, Biman C., primary, Kriley, Isaac, primary, Schrump, David S., primary, and Rosenberg, Steven A., primary

Published
2023
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24. Supplementary Table 3 from Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer

Author

Lo, Winifred, primary, Parkhurst, Maria, primary, Robbins, Paul F., primary, Tran, Eric, primary, Lu, Yong-Chen, primary, Jia, Li, primary, Gartner, Jared J., primary, Pasetto, Anna, primary, Deniger, Drew, primary, Malekzadeh, Parisa, primary, Shelton, Thomas E., primary, Prickett, Todd, primary, Ray, Satyajit, primary, Kivitz, Scott, primary, Paria, Biman C., primary, Kriley, Isaac, primary, Schrump, David S., primary, and Rosenberg, Steven A., primary

Published
2023
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25. Supplementary Tables 1 and 2 from Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer

Author

Lo, Winifred, primary, Parkhurst, Maria, primary, Robbins, Paul F., primary, Tran, Eric, primary, Lu, Yong-Chen, primary, Jia, Li, primary, Gartner, Jared J., primary, Pasetto, Anna, primary, Deniger, Drew, primary, Malekzadeh, Parisa, primary, Shelton, Thomas E., primary, Prickett, Todd, primary, Ray, Satyajit, primary, Kivitz, Scott, primary, Paria, Biman C., primary, Kriley, Isaac, primary, Schrump, David S., primary, and Rosenberg, Steven A., primary

Published
2023
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26. 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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27. Data from Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer

Author

Lo, Winifred, primary, Parkhurst, Maria, primary, Robbins, Paul F., primary, Tran, Eric, primary, Lu, Yong-Chen, primary, Jia, Li, primary, Gartner, Jared J., primary, Pasetto, Anna, primary, Deniger, Drew, primary, Malekzadeh, Parisa, primary, Shelton, Thomas E., primary, Prickett, Todd, primary, Ray, Satyajit, primary, Kivitz, Scott, primary, Paria, Biman C., primary, Kriley, Isaac, primary, Schrump, David S., primary, and Rosenberg, Steven A., primary

Published
2023
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28. 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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29. 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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30. 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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31. 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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32. 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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33. Breast Cancers Are Immunogenic: Immunologic Analyses and a Phase II Pilot Clinical Trial Using Mutation-Reactive Autologous Lymphocytes

Author

Zacharakis, Nikolaos, primary, Huq, Lutfi M., additional, Seitter, Samantha J., additional, Kim, Sanghyun P., additional, Gartner, Jared J., additional, Sindiri, Sivasish, additional, Hill, Victoria K., additional, Li, Yong F., additional, Paria, Biman C., additional, Ray, Satyajit, additional, Gasmi, Billel, additional, Lee, Chyi-chia, additional, Prickett, Todd D., additional, Parkhurst, Maria R., additional, Robbins, Paul F., additional, Langhan, Michelle M., additional, Shelton, Thomas E., additional, Parikh, Anup Y., additional, Levi, Shoshana T., additional, Hernandez, Jonathan M., additional, Hoang, Chuong D., additional, Sherry, Richard M., additional, Yang, James C., additional, Feldman, Steven A., additional, Goff, Stephanie L., additional, and Rosenberg, Steven A., additional

Published
2022
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34. 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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35. 167 High-efficiency capture of anti-tumor neoantigen-reactive T cell receptors from tumor digest

Author

Chatani, Praveen, primary, Lowery, Frank, additional, Parikh, Neilesh, additional, Yossef, Rami, additional, Hill, Victoria, additional, Yu, Zhiya, additional, Prickett, Todd, additional, Gartner, Jared, additional, Paria, Biman, additional, Ray, Satyajit, additional, Florentin, Maria, additional, Robbins, Paul, additional, Krishna, Sri, additional, and Rosenberg, Steven, additional

Published
2021
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36. Un film est né.

Author

Ray, Satyajit

Abstract

A personal narrative is presented which explores the author's experience during the first day of shooting for his film "Pather Panchali" (La Complainte du Sentier or The Song of the Little Road).

Published
2023

37. An Unusual Cause of Hemorrhagic Cystitis in a Teenager With Medulloblastoma

Author

Slack, Daniel, Ray, Satyajit, Lee, Boma, and Sastry, Jairam

Abstract

Hemorrhagic cystitis is a life-threatening condition in which the transitional epithelium and blood vessels of the bladder necrose leading to severe hematuria, abdominal pain, and voiding lower urinary tract symptoms. Etiology includes chemotherapy (cyclophosphamide, ifosfamide, busulfan), radiotherapy, or infectious agents. We present a pediatric case of a 15-year-old boy with medulloblastoma who developed hemorrhagic cystitis following cisplatin chemotherapy. All other causes were ruled out and it is therefore likely that the agent, in this case, was cisplatin, which has never had hemorrhagic cystitis reported as a side effect. We also suggest a mechanism for urothelial injury centered around OCT-2 receptors.

Published
2024
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38. Neoantigen-specific stimulation of tumor-infiltrating lymphocytes enables effective TCR isolation and expansion while preserving stem-like memory phenotypes.

Author

Levin N, Kim SP, Marquardt CA, Vale NR, Yu Z, Sindiri S, Gartner JJ, Parkhurst M, Krishna S, Lowery FJ, Zacharakis N, Levy L, Prickett TD, Benzine T, Ray S, Masi RV, Gasmi B, Li Y, Islam R, Bera A, Goff SL, Robbins PF, and Rosenberg SA

Subjects
Humans, Mice, Immunologic Memory, Animals, Female, Phenotype, Neoplasms immunology, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Antigens, Neoplasm immunology, Receptors, Antigen, T-Cell immunology, Receptors, Antigen, T-Cell metabolism
Abstract

Background: Tumor-infiltrating lymphocytes (TILs) targeting neoantigens can effectively treat a selected set of metastatic solid cancers. However, harnessing TILs for cancer treatments remains challenging because neoantigen-reactive T cells are often rare and exhausted, and ex vivo expansion can further reduce their frequencies. This complicates the identification of neoantigen-reactive T-cell receptors (TCRs) and the development of TIL products with high reactivity for patient treatment., Methods: We tested whether TILs could be in vitro stimulated against neoantigens to achieve selective expansion of neoantigen-reactive TILs. Given their prevalence, mutant p53 or RAS were studied as models of human neoantigens. An in vitro stimulation method, termed "NeoExpand", was developed to provide neoantigen-specific stimulation to TILs. 25 consecutive patient TILs from tumors harboring p53 or RAS mutations were subjected to NeoExpand., Results: We show that neoantigenic stimulation achieved selective expansion of neoantigen-reactive TILs and broadened the neoantigen-reactive CD4 + and CD8 + TIL clonal repertoire. This allowed the effective isolation of novel neoantigen-reactive TCRs. Out of the 25 consecutive TIL samples, neoantigenic stimulation enabled the identification of 16 unique reactivities and 42 TCRs, while conventional TIL expansion identified 9 reactivities and 14 TCRs. Single-cell transcriptome analysis revealed that neoantigenic stimulation increased neoantigen-reactive TILs with stem-like memory phenotypes expressing IL-7R, CD62L, and KLF2. Furthermore, neoantigenic stimulation improved the in vivo antitumor efficacy of TILs relative to the conventional OKT3-induced rapid TIL expansion in p53-mutated or KRAS-mutated xenograft mouse models., Conclusions: Taken together, neoantigenic stimulation of TILs selectively expands neoantigen-reactive TILs by frequencies and by their clonal repertoire. NeoExpand led to improved phenotypes and functions of neoantigen-reactive TILs. Our data warrant its clinical evaluation., Trial Registration Number: NCT00068003, NCT01174121, and NCT03412877., Competing Interests: Competing interests: NL, SPK and SAR have a pending patent application. The rest of the authors report no competing interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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39. Cell surface marker-based capture of neoantigen-reactive CD8 + T-cell receptors from metastatic tumor digests.

Author

Chatani PD, Lowery FJ, Parikh NB, Hitscherich KJ, Yossef R, Hill V, Gartner JJ, Paria B, Florentin M, Ray S, Bera A, Parkhust M, Robbins P, Krishna S, and Rosenberg SA

Subjects
Humans, CD8-Positive T-Lymphocytes, Receptors, Antigen, T-Cell, Lymphocytes, Tumor-Infiltrating, Antigens, Neoplasm, Neoplasms metabolism
Abstract

Background: Cellular immunotherapies using autologous tumor-infiltrating lymphocytes (TIL) can induce durable regression of epithelial cancers in selected patients with treatment-refractory metastatic disease. As the genetic engineering of T cells with tumor-reactive T-cell receptors (TCRs) comes to the forefront of clinical investigation, the rapid, scalable, and cost-effective detection of patient-specific neoantigen-reactive TIL remains a top priority., Methods: We analyzed the single-cell transcriptomic states of 31 neoantigen-specific T-cell clonotypes to identify cell surface dysfunction markers that best identified the metastatic transcriptional states enriched with antitumor TIL. We developed an efficient method to capture neoantigen-reactive TCRs directly from resected human tumors based on cell surface co-expression of CD39, programmed cell death protein-1, and TIGIT dysfunction markers (CD8 + TIL TP )., Results: TIL TP TCR isolation achieved a high degree of correlation with single-cell transcriptomic signatures that identify neoantigen-reactive TCRs, making it a cost-effective strategy using widely available resources. Reconstruction of additional TIL TP TCRs from tumors identified known and novel antitumor TCRs, showing that at least 39.5% of TIL TP TCRs are neoantigen-reactive or tumor-reactive. Despite their substantial enrichment for neoantigen-reactive TCR clonotypes, clonal dynamics of 24 unique antitumor TIL TP clonotypes from four patients indicated that most in vitro expanded TIL TP populations failed to demonstrate neoantigen reactivity, either by loss of neoantigen-reactive clones during TIL expansion, or through functional impairment during cognate neoantigen recognition., Conclusions: While direct usage of in vitro-expanded CD8 + TIL TP as a source for cellular therapy might be precluded by profound TIL dysfunction, isolating TIL TP represents a streamlined effective approach to rapidly identify neoantigen-reactive TCRs to design engineered cellular immunotherapies against cancer., Competing Interests: Competing interests: FJL, SK, PR, and SAR are listed on an international patent application filed based on the NeoTCR8 signature described in this study. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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