Article
Oncology
MacLean S. Hall, Jamie K. Teer, Xiaoqing Yu, Holly Branthoover, Sebastian Snedal, Madeline Rodriguez-Valentin, Luz Nagle, Ellen Scott, Ben Schachner, Patrick Innamarato, Amy M. Hall, Jamie Blauvelt, Carolyn J. Rich, Allison D. Richards, Jake Ceccarelli, T. J. Langer, Sean J. Yoder, Matthew S. Beatty, Cheryl A. Cox, Jane L. Messina, Daniel Abate-Daga, James J. Mule, John E. Mullinax, Amod A. Sarnaik, Shari Pilon-Thomas
Summary: This study highlights the importance of neoantigen-specific CD4(+)T cells within tumor-infiltrating lymphocytes (TILs) as a potent source of tumor-specific effectors. The findings suggest that these CD4(+)T cells play a significant role in antitumor immunity and should be included in future adoptive cell therapy (ACT) protocols to improve treatment efficacy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Yong-Chen Lu, Zhili Zheng, Frank J. Lowery, Jared J. Gartner, Todd D. Prickett, Paul F. Robbins, Steven A. Rosenberg
Summary: Recognition of neoantigens by T cells is important in cancer immunotherapy, and identifying neoantigen-specific TCRs is crucial for studying T cell responses and modifying T cell specificity. A new process using single-cell sequencing was developed to isolate neoantigen-specific TCR sequences, successfully identifying 28 such TCRs from melanoma and colorectal tumor specimens. This approach offers an efficient way to isolate antigen-specific TCRs for research and clinical use.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Praveen D. Chatani, Frank J. Lowery, Neilesh B. Parikh, Kyle J. Hitscherich, Rami Yossef, Victoria Hill, Jared J. Gartner, Biman Paria, Maria Florentin, Satyajit Ray, Alakesh Bera, Maria Parkhust, Paul Robbins, Sri Krishna, Steven A. Rosenberg
Summary: By analyzing the single-cell transcriptomic states of neoantigen-specific T-cell clonotypes, researchers identified dysfunction markers on the cell surface that can best identify the transcriptional states enriched with antitumor T-cells. They developed an efficient method to capture neoantigen-reactive T-cell receptors (TCRs) directly from resected human tumors. The isolation of TIL(TP) TCRs showed a high correlation with single-cell transcriptomic signatures for neoantigen-reactive TCRs, making it a cost-effective strategy using widely available resources.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Samantha M. Fix, Marie-Andree Forget, Donastas Sakellariou-Thompson, Yunfei Wang, Tamara M. Griffiths, Minjung Lee, Cara L. Haymaker, Ana Lucia Dominguez, Rafet Basar, Christopher Reyes, Sanjay Kumar, Larissa A. Meyer, Patrick Hwu, Chantale Bernatchez, Amir A. Jazaeri
Summary: In this study, we optimized CRISPR/Cas9-mediated knockout of TGF-beta receptor 2 (TGFBR2) in patient-derived ovarian cancer TIL. TGFBR2 knockout TIL showed resistance to immunosuppression and improved cytotoxicity. This lays the groundwork for clinical translation of CRISPR-modified TIL for the treatment of ovarian cancer and other solid cancers.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Julia Karbach, Dragan Kiselicki, Kathrin Brand, Claudia Wahle, Evgueni Sinelnikov, Dirk Gustavus, Hans Hoffmeister, Hans-Bernd Prisack, Akin Atmaca, Elke Jaeger
Summary: Adoptive transfer of autologous tumor-specific lymphocytes in conjunction with IL-2 and immune-checkpoint blockade led to complete and durable tumor remission in a patient with metastatic hormone-refractory NY-ESO-1 expressing prostate cancer. The treatment resulted in a decrease of tumor-driven NY-ESO-1 serum antibody and prostate-specific antigen, demonstrating the effectiveness of this method for advanced malignancies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Anders Handrup Kverneland, Christopher Aled Chamberlain, Troels Holz Borch, Morten Nielsen, Sofie Kirial Mork, Julie Westerlin Kjeldsen, Cathrine Lund Lorentzen, Lise Pyndt Jorgensen, Lene Buhl Riis, Christina Westmose Yde, Ozcan Met, Marco Donia, Inge Marie Svane
Summary: This study demonstrated high success rates of TIL expansion and tumor regressions in multiple solid cancer types when combining TIL ACT with CPIs. In vitro tumor reactivity was positively associated with treatment outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Natalia Plewa, Lucia Poncette, Thomas Blankenstein
Summary: This study suggests that HLA-DR4-restricted TCRs specific for the TGF beta R2(-1) recurrent neoantigen could be valuable candidates for adoptive T cell therapy in cancer patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Teng Wei, Matthias Leisegang, Ming Xia, Kazuma Kiyotani, Ning Li, Chenquan Zeng, Chunyan Deng, Jinxing Jiang, Makiko Harada, Nishant Agrawal, Liangping Li, Hui Qi, Yusuke Nakamura, Lili Ren
Summary: This study explores the use of TCR-engineered T cells in adoptive cell therapy for treating relapsed and metastatic cancers, by utilizing blood-derived T cells and HLA-matched APCs to overcome challenges in isolating PBMCs from advanced-stage cancer patients. The established protocol provides flexibility in identifying neoantigen-specific TCRs when patient PBMCs and tumor material are not available.
Article
Oncology
Chaoting Zhang, Yizhe Sun, Shance Li, Luyan Shen, Xia Teng, Yefei Xiao, Nan Wu, Zheming Lu
Summary: The study found that restoring autophagic flux of exhausted TILs through spermidine treatment can enhance the diversity of TCR repertoire, reduce the expression of inhibitory immunoreceptors (PD1, TIM3, or LAG3), improve proliferation and effector functions, leading to superior in vitro and in vivo antitumor activity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Eric Tran
Summary: The goal of cancer therapeutics is to destroy cancer cells while minimizing damage to normal cells. Immunological targeting of neoantigens, which are mutated peptide antigens specifically recognized by T cells, offers a safe and promising strategy for cancer treatment. This article reviews the clinical application of adoptive cell therapy targeting neoantigens in patients with epithelial cancers.
Review
Biology
Dongdong Ti, Miaomiao Bai, Xiaolei Li, Jianshu Wei, Deyun Chen, Zhiqiang Wu, Yao Wang, Weidong Han
Summary: Impaired tumor-specific effector T cells lead to tumor progression and unfavorable clinical outcomes, but adoptive T cell therapy (ACT) has emerged as a promising strategy in cancer treatment, involving ex vivo stimulation and expansion of tumor-infiltrating lymphocytes or genetically modified T cells to provide efficient and long-lasting immune defense against transformed cells.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Article
Oncology
Vid Leko, Gal Cafri, Rami Yossef, Biman Paria, Victoria Hill, Devikala Gurusamy, Zhili Zheng, Jared J. Gartner, Todd D. Prickett, Stephanie L. Goff, Paul Robbins, Yong-Chen Lu, Steven A. Rosenberg
Summary: By stimulating patient blood-derived memory T cells in vitro, researchers found that in a cohort of five patients with glioblastoma, circulating CD4(+) memory T cells from one patient specifically recognized a cancer neoantigen harboring a mutation in the EED gene that was unique to that patient's tumor. This finding suggests the potential for isolating neoantigen-reactive T cells from patients with glioblastoma and further developing neoantigen-directed adoptive T cell therapy for this disease.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Ahmet Murat Aydin, MacLean Hall, Brittany L. Bunch, Holly Branthoover, Zachary Sannasardo, Amy Mackay, Matthew Beatty, Amod A. Sarnaik, John E. Mullinax, Philippe E. Spiess, Shari Pilon-Thomas
Summary: This study demonstrated successful expansion of tumor-reactive TIL from penile cancer patients, supporting the development of ACT strategies using TIL for the treatment of advanced and recurrent penile cancer.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Oncology
Masahiro Matsuki, Yoshihiko Hirohashi, Munehide Nakatsugawa, Aiko Murai, Terufumi Kubo, Shinichi Hashimoto, Serina Tokita, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Sachiyo Nishida, Toshiaki Tanaka, Hiroshi Kitamura, Naoya Masumori, Toshihiko Torigoe
Summary: ICIs are used in cancer immunotherapy to block certain pathways, but low response rates and tumor heterogeneity can lead to resistance. This study found that the specificity of TILs in RCC may be related to gene mutations and reactivity, suggesting heterogenous tumors may have diverse gene mutations and responses to TILs.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Jitendra Kumar, Ritesh Kumar, Amir Kumar Singh, Elviche L. Tsakem, Mahesh Kathania, Matthew J. Riese, Arianne L. Theiss, Marco L. Davila, K. Venuprasad
Summary: The study identified Cbl-b as a potential target for overcoming exhausted CAR T-cell function in solid tumors. Inhibition of Cbl-b restored effector function of exhausted T cells. Depletion of Cbl-b enhanced CAR T-cell efficacy in reducing tumor growth, decreasing exhausted T cells, and increasing effector cytokine expression.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)