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Your search keyword '"Hizra Farrukh"' showing total 5 results
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5 results on '"Hizra Farrukh"'

1. Increasing cure rates of solid tumors by immune checkpoint inhibitors

Author

Weijie Ma, Ruobing Xue, Zheng Zhu, Hizra Farrukh, Wenru Song, Tianhong Li, Lei Zheng, and Chong-xian Pan

Subjects
Immunotherapy, Immune checkpoint inhibitor, Neoadjuvant therapy, Adjuvant therapy, Lung cancer, Gastrointestinal cancers, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Immunotherapy has become the central pillar of cancer therapy. Immune checkpoint inhibitors (ICIs), a major category of tumor immunotherapy, reactivate preexisting anticancer immunity. Initially, ICIs were approved only for advanced and metastatic cancers in the salvage setting after or concurrent with chemotherapy at a response rate of around 20–30% with a few exceptions. With significant progress over the decade, advances in immunotherapy have led to numerous clinical trials investigating ICIs as neoadjuvant and/or adjuvant therapies for resectable solid tumors. The promising results of these trials have led to the United States Food and Drug Administration (FDA) approvals of ICIs as neoadjuvant or adjuvant therapies for non-small cell lung cancer, melanoma, triple-negative breast cancer, and bladder cancer, and the list continues to grow. This therapy represents a paradigm shift in cancer treatment, as many early-stage cancer patients could be cured with the introduction of immunotherapy in the early stages of cancer. Therefore, this topic became one of the main themes at the 2021 China Cancer Immunotherapy Workshop co-organized by the Chinese American Hematologist and Oncologist Network, the China National Medical Products Administration and the Tsinghua University School of Medicine. This review article summarizes the current landscape of ICI-based immunotherapy, emphasizing the new clinical developments of ICIs as curative neoadjuvant and adjuvant therapies for early-stage disease.

Published
2023
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2. CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy

Author

Kevin Pan, Hizra Farrukh, Veera Chandra Sekhar Reddy Chittepu, Huihong Xu, Chong-xian Pan, and Zheng Zhu

Subjects
Chimeric antigen receptor (CAR), CAR macrophage, CAR T therapy, CAR NK cells, Adoptive cell transfer, Immunotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Adoptive cell therapy with chimeric antigen receptor (CAR) immunotherapy has made tremendous progress with five CAR T therapies approved by the US Food and Drug Administration for hematological malignancies. However, CAR immunotherapy in solid tumors lags significantly behind. Some of the major hurdles for CAR immunotherapy in solid tumors include CAR T cell manufacturing, lack of tumor-specific antigens, inefficient CAR T cell trafficking and infiltration into tumor sites, immunosuppressive tumor microenvironment (TME), therapy-associated toxicity, and antigen escape. CAR Natural Killer (NK) cells have several advantages over CAR T cells as the NK cells can be manufactured from pre-existing cell lines or allogeneic NK cells with unmatched major histocompatibility complex (MHC); can kill cancer cells through both CAR-dependent and CAR-independent pathways; and have less toxicity, especially cytokine-release syndrome and neurotoxicity. At least one clinical trial showed the efficacy and tolerability of CAR NK cell therapy. Macrophages can efficiently infiltrate into tumors, are major immune regulators and abundantly present in TME. The immunosuppressive M2 macrophages are at least as efficient as the proinflammatory M1 macrophages in phagocytosis of target cells; and M2 macrophages can be induced to differentiate to the M1 phenotype. Consequently, there is significant interest in developing CAR macrophages for cancer immunotherapy to overcome some major hurdles associated with CAR T/NK therapy, especially in solid tumors. Nevertheless, both CAR NK and CAR macrophages have their own limitations. This comprehensive review article will discuss the current status and the major hurdles associated with CAR T and CAR NK therapy, followed by the structure and cutting-edge research of developing CAR macrophages as cancer-specific phagocytes, antigen presenters, immunostimulators, and TME modifiers.

Published
2022
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3. Supplementary Figure from Phototherapy with Cancer-Specific Nanoporphyrin Potentiates Immunotherapy in Bladder Cancer

Author

Chong-xian Pan, Kit S. Lam, Yuanpei Li, Rao Prabhala, Veera Chandra Sekhar Reddy Chittepu, Zhixiu Cao, Ruan Yuan, Wei Shi, Shaoming Zhu, Hizra Farrukh, Xiangdong Xue, Tzu-Yin Lin, Hongyong Zhang, Ai-Hong Ma, and Zheng Zhu

Abstract

Supplementary Figure from Phototherapy with Cancer-Specific Nanoporphyrin Potentiates Immunotherapy in Bladder Cancer

Published
2023
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4. Data from Phototherapy with Cancer-Specific Nanoporphyrin Potentiates Immunotherapy in Bladder Cancer

Author

Chong-xian Pan, Kit S. Lam, Yuanpei Li, Rao Prabhala, Veera Chandra Sekhar Reddy Chittepu, Zhixiu Cao, Ruan Yuan, Wei Shi, Shaoming Zhu, Hizra Farrukh, Xiangdong Xue, Tzu-Yin Lin, Hongyong Zhang, Ai-Hong Ma, and Zheng Zhu

Abstract

Purpose:Immune checkpoint inhibitors (ICI) in general have shown poor efficacy in bladder cancer. The purpose of this project was to determine whether photodynamic therapy (PDT) with bladder cancer–specific porphyrin-based PLZ4-nanoparticles (PNP) potentiated ICI.Experimental Design:SV40 T/Ras double-transgenic mice bearing spontaneous bladder cancer and C57BL/6 mice carrying syngeneic bladder cancer models were used to determine the efficacy and conduct molecular correlative studies.Results:PDT with PNP generated reactive oxygen species, and induced protein carbonylation and dendritic cell maturation. In SV40 T/Ras double-transgenic mice carrying spontaneous bladder cancer, the median survival was 33.7 days in the control, compared with 44.8 (P = 0.0123), 52.6 (P = 0.0054), and over 75 (P = 0.0001) days in the anti-programmed cell death-1 antibody (anti-PD-1), PNP PDT, and combination groups, respectively. At Day 75 when all mice in other groups died, only 1 in 7 mice in the combination group died. For the direct anti-tumor activity, compared with the control, the anti-PD-1, PNP PDT, and combination groups induced a 40.25% (P = 0.0003), 80.72% (P < 0.0001), and 93.03% (P < 0.0001) tumor reduction, respectively. For the abscopal anticancer immunity, the anti-PD-1, PNP PDT, and combination groups induced tumor reduction of 45.73% (P = 0.0001), 54.92% (P < 0.0001), and 75.96% (P < 0.0001), respectively. The combination treatment also diminished spontaneous and induced lung metastasis. Potential of immunotherapy by PNP PDT is multifactorial.Conclusions:In addition to its potential for photodynamic diagnosis and therapy, PNP PDT can synergize immunotherapy in treating locally advanced and metastatic bladder cancer. Clinical trials are warranted to determine the efficacy and toxicity of this combination.

Published
2023
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5. Phototherapy with Cancer-Specific Nanoporphyrin Potentiates Immunotherapy in Bladder Cancer

Author

Zheng Zhu, Ai-Hong Ma, Hongyong Zhang, Tzu-Yin Lin, Xiangdong Xue, Hizra Farrukh, Shaoming Zhu, Wei Shi, Ruan Yuan, Zhixiu Cao, Veera Chandra Sekhar Reddy Chittepu, Rao Prabhala, Yuanpei Li, Kit S. Lam, and Chong-xian Pan

Subjects
Urologic Diseases, Cancer Research, Tumor, Oncology and Carcinogenesis, Mice, Transgenic, Phototherapy, Inbred C57BL, Article, Transgenic, Cell Line, Mice, Inbred C57BL, Vaccine Related, Mice, Oncology, Photochemotherapy, Urinary Bladder Neoplasms, 5.1 Pharmaceuticals, Cell Line, Tumor, Animals, Immunologic Factors, Immunization, Immunotherapy, Oncology & Carcinogenesis, Development of treatments and therapeutic interventions, Cancer
Abstract

Purpose: Immune checkpoint inhibitors (ICI) in general have shown poor efficacy in bladder cancer. The purpose of this project was to determine whether photodynamic therapy (PDT) with bladder cancer–specific porphyrin-based PLZ4-nanoparticles (PNP) potentiated ICI. Experimental Design: SV40 T/Ras double-transgenic mice bearing spontaneous bladder cancer and C57BL/6 mice carrying syngeneic bladder cancer models were used to determine the efficacy and conduct molecular correlative studies. Results: PDT with PNP generated reactive oxygen species, and induced protein carbonylation and dendritic cell maturation. In SV40 T/Ras double-transgenic mice carrying spontaneous bladder cancer, the median survival was 33.7 days in the control, compared with 44.8 (P = 0.0123), 52.6 (P = 0.0054), and over 75 (P = 0.0001) days in the anti-programmed cell death-1 antibody (anti-PD-1), PNP PDT, and combination groups, respectively. At Day 75 when all mice in other groups died, only 1 in 7 mice in the combination group died. For the direct anti-tumor activity, compared with the control, the anti-PD-1, PNP PDT, and combination groups induced a 40.25% (P = 0.0003), 80.72% (P < 0.0001), and 93.03% (P < 0.0001) tumor reduction, respectively. For the abscopal anticancer immunity, the anti-PD-1, PNP PDT, and combination groups induced tumor reduction of 45.73% (P = 0.0001), 54.92% (P < 0.0001), and 75.96% (P < 0.0001), respectively. The combination treatment also diminished spontaneous and induced lung metastasis. Potential of immunotherapy by PNP PDT is multifactorial. Conclusions: In addition to its potential for photodynamic diagnosis and therapy, PNP PDT can synergize immunotherapy in treating locally advanced and metastatic bladder cancer. Clinical trials are warranted to determine the efficacy and toxicity of this combination.

Published
2022

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