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Fine-tuning the antigen sensitivity of CAR T cells: emerging strategies and current challenges

Frontiers in Immunology, 2023
Chimeric antigen receptor (CAR) T cells are “living drugs” that specifically recognize their target antigen through an antibody-derived binding domain resulting in T cell activation, expansion, and destruction of cognate target cells.
Dennis Christoph Harrer, Dennis Christoph Harrer, Sin-Syue Li, Sin-Syue Li, Marcell Kaljanac, Markus Barden, Hong Pan, Hinrich Abken   +7 more
doaj   +1 more source

CAR Triggered Release of Type-1 Interferon Limits CAR T-Cell Activities by an Artificial Negative Autocrine Loop

Cells, 2022
The advent of chimeric antigen receptor (CAR) T cells expedited the field of cancer immunotherapy enabling durable remissions in patients with refractory hematological malignancies.
Dennis Christoph Harrer, Charlotte Schenkel, Valerie Bezler, Marcell Kaljanac, Jordan Hartley, Markus Barden, Hong Pan, Astrid Holzinger, Wolfgang Herr, Hinrich Abken   +9 more
doaj   +1 more source

Anti-TACI single and dual-targeting CAR T cells overcome BCMA antigen loss in multiple myeloma

Nature Communications, 2023
Chimeric Antigen Receptor (CAR) T cells directed to B cell maturation antigen (BCMA) mediate profound responses in patients with multiple myeloma, but most patients do not achieve long-term complete remissions.
Rebecca C. Larson, Michael C. Kann, Charlotte Graham, Christopher W. Mount, Ana P. Castano, Won-Ho Lee, Amanda A. Bouffard, Hana N. Takei, Antonio J. Almazan, Irene Scarfó, Trisha R. Berger, Andrea Schmidts, Matthew J. Frigault, Kathleen M. E. Gallagher, Marcela V. Maus   +14 more
doaj   +1 more source

The loss of B7-H4 expression in breast cancer cells escaping from T cell cytotoxicity contributes to epithelial-to-mesenchymal transition

Breast Cancer Research, 2023
Background B7 homology 4 (B7-H4), a potential target for cancer therapy, has been demonstrated to inhibit T cell cytotoxicity in the early stages of breast cancer.
Linlin Zhou, Jichun Wu, Mei Ruan, Yonglei Xiao, Hailin Lan, Qiongwen Wu, Chen-Wei Yu, Qiuyu Zhang   +7 more
doaj   +1 more source

Intratumoral co‐injection of NK cells and NKG2A‐neutralizing monoclonal antibodies

EMBO Molecular Medicine, 2023
NK‐cell reactivity against cancer is conceivably suppressed in the tumor microenvironment by the interaction of the inhibitory receptor NKG2A with the non‐classical MHC‐I molecules HLA‐E in humans or Qa‐1b in mice.
Ignacio Melero, Maria C Ochoa, Carmen Molina, Sandra Sanchez‐Gregorio, Saray Garasa, Carlos Luri‐Rey, Sandra Hervas‐Stubbs, Noelia Casares, Edurne Elizalde, Gabriel Gomis, Assunta Cirella, Pedro Berraondo, Alvaro Teijeira, Maite Alvarez   +13 more
doaj   +1 more source

IRF4 downregulation improves sensitivity and endurance of CAR T cell functional capacities

Frontiers in Immunology, 2023
Chimeric antigen receptor (CAR) modified T cells can induce complete remissions in patients with advanced hematological malignancies. Nevertheless, the efficacy is mostly transient and remains so far poor in the treatment of solid tumors.
Dennis Christoph Harrer, Dennis Christoph Harrer, Valerie Bezler, Jordan Hartley, Wolfgang Herr, Hinrich Abken   +5 more
doaj   +1 more source

Induction of tier-2 neutralizing antibodies in mice with a DNA-encoded HIV envelope native like trimer

Nature Communications, 2022
HIV envelope is a target for vaccine development, but induction of broadly neutralizing antibodies has been difficult. Here, the authors show that electroporation with a synthetic DNA vaccine construct allows in vivo production of HIV envelope native ...
Ziyang Xu, Susanne Walker, Megan C. Wise, Neethu Chokkalingam, Mansi Purwar, Alan Moore, Edgar Tello-Ruiz, Yuanhan Wu, Sonali Majumdar, Kylie M. Konrath, Abhijeet Kulkarni, Nicholas J. Tursi, Faraz I. Zaidi, Emma L. Reuschel, Ishaan Patel, April Obeirne, Jianqiu Du, Katherine Schultheis, Lauren Gites, Trevor Smith, Janess Mendoza, Kate E. Broderick, Laurent Humeau, Jesper Pallesen, David B. Weiner, Daniel W. Kulp   +25 more
doaj   +1 more source

Intracavitary adoptive transfer of IL-12 mRNA-engineered tumor-specific CD8+ T cells eradicates peritoneal metastases in mouse models

OncoImmunology, 2023
Previous studies have shown that local delivery of tumor antigen-specific CD8+ T lymphocytes engineered to transiently express single-chain IL-12 mRNA is highly efficacious.
Claudia Augusta Di Trani, Assunta Cirella, Leire Arrizabalaga, Ángela Bella, Myriam Fernandez-Sendin, Joan Salvador Russo-Cabrera, Celia Gomar, Irene Olivera, Elizabeth Bolaños, José González-Gomariz, Maite Álvarez, Iñaki Etxeberria, Belen Palencia, Álvaro Teijeira, Ignacio Melero, Pedro Berraondo, Fernando Aranda   +16 more
doaj   +1 more source

Expression of TIM3/VISTA checkpoints and the CD68 macrophage-associated marker correlates with anti-PD1/PDL1 resistance: implications of immunogram heterogeneity. [PDF]

, 2020
Although immunotherapies have achieved remarkable salutary effects among subgroups of advanced cancers, most patients do not respond. We comprehensively evaluated biomarkers associated with the "cancer-immunity cycle" in the pan-cancer setting in order ...
Dressman, Devin, Eskander, Ramez, Glenn, Sean T, Goodman, Aaron, Ikeda, Sadakatsu, Kato, Shumei, Kumaki, Yuichi, Kurzrock, Razelle, Lee, Suzanna, Lenzo, Felicia L, Morrison, Carl, Nikanjam, Mina, Okamura, Ryosuke, Papanicolau-Sengos, Antonios   +13 more
core   +1 more source

CAR T cell therapy becomes CHIC: “cytokine help intensified CAR” T cells

Frontiers in Immunology, 2023
Chimeric antigen receptors (CARs) in the canonical “second generation” format provide two signals for inducing T cell effector functions; the primary “signal-1” is provided through the TCR CD3ζ chain and the “signal-2” through a linked costimulatory ...
Simone Thomas, Simone Thomas, Hinrich Abken, Hinrich Abken   +3 more
doaj   +1 more source