Bispecific Antibody Format and the Organization of Immunological Synapses in T Cell-Redirecting Strategies for Cancer Immunotherapy

Carrasco-Padilla, Carlos; Hernaiz-Esteban, Alicia; Álvarez‐Vallina, Luís; Aguilar-Sopeña, Óscar; Roda-Navarro, Pedro

doi:10.3390/pharmaceutics15010132

Cited by 9 publications

(2 citation statements)

References 89 publications

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“…This may relate to the TCR-T and CAR-T forming different immunologic synapses. 30 Collectively, these data provided evidence that TAEST16001 cell treatment was safe when used with modified lymphodepletion and low-dose IL-2.…”

Section: Discussionmentioning

confidence: 85%

Phase 1 clinical trial to assess safety and efficacy of NY-ESO-1-specific TCR T cells in HLA-A∗02:01 patients with advanced soft tissue sarcoma

Pan

Weng

Liu

et al. 2023

Cell Reports Medicine

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Section: Discussionmentioning

confidence: 85%

Phase 1 clinical trial to assess safety and efficacy of NY-ESO-1-specific TCR T cells in HLA-A∗02:01 patients with advanced soft tissue sarcoma

Pan

Weng

Liu

et al. 2023

Cell Reports Medicine

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“…These molecules work by binding to TCR complex proteins such as CD3 and a common tumor antigen, thus engaging tumor and T cells ( Huehls et al, 2015 ). Hence, they elicit a polyclonal CTL response that is not restricted by TCR specificity and surface presentation of tumor-peptide/MHC class I complexes ( Carrasco-Padilla et al, 2022 ). Although biAbs efficiently elicit an immune response against cancer cells in vitro ( Deisting et al, 2015 ) and in vivo ( Zhao et al, 2019 ), their clinical application is often limited, partially because of the expression of pro-survival factors protecting tumor cells from T cell–induced apoptosis ( Tuomela et al, 2022 ; Kaloni et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Nucleolar protein TAAP1/C22orf46confers pro-survival signaling in non-small cell lung cancer

Döring,

Brux,

Paszkowski-Rogacz

et al. 2024

Life Sci. Alliance

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Tumor cells subvert immune surveillance or lytic stress by harnessing inhibitory signals. Hence, bispecific antibodies have been developed to direct CTLs to the tumor site and foster immune-dependent cytotoxicity. Although applied with success, T cell–based immunotherapies are not universally effective partially because of the expression of pro-survival factors by tumor cells protecting them from apoptosis. Here, we report a CRISPR/Cas9 screen in human non-small cell lung cancer cells designed to identify genes that confer tumors with the ability to evade the cytotoxic effects of CD8+T lymphocytes engaged by bispecific antibodies. We show that the geneC22orf46facilitates pro-survival signals and that tumor cells devoid ofC22orf46expression exhibit increased susceptibility to T cell–induced apoptosis and stress by genotoxic agents. Although annotated as a non-coding gene, we demonstrate thatC22orf46encodes a nucleolar protein, hereafter referred to as “Tumor Apoptosis Associated Protein 1,” up-regulated in lung cancer, which displays remote homologies to the BH domain containing Bcl-2 family of apoptosis regulators. Collectively, the findings establish TAAP1/C22orf46as a pro-survival oncogene with implications to therapy.

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Therapeutic antibodies in oncology: an immunopharmacological overview

Toledo-Stuardo,

Ribeiro,

González-Herrera

et al. 2024

Cancer Immunol Immunother

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The biotechnological development of monoclonal antibodies and their immunotherapeutic use in oncology have grown exponentially in the last decade, becoming the first-line therapy for some types of cancer. Their mechanism of action is based on the ability to regulate the immune system or by interacting with targets that are either overexpressed in tumor cells, released into the extracellular milieu or involved in processes that favor tumor growth. In addition, the intrinsic characteristics of each subclass of antibodies provide specific effector functions against the tumor by activating antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, among other mechanisms. The rational design and engineering of monoclonal antibodies have improved their pharmacokinetic and pharmacodynamic features, thus optimizing the therapeutic regimens administered to cancer patients and improving their clinical outcomes. The selection of the immunoglobulin G subclass, modifications to its crystallizable region (Fc), and conjugation of radioactive substances or antineoplastic drugs may all improve the antitumor effects of therapeutic antibodies. This review aims to provide insights into the immunological and pharmacological aspects of therapeutic antibodies used in oncology, with a rational approach at molecular modifications that can be introduced into these biological tools, improving their efficacy in the treatment of cancer. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-024-03814-2.

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Bispecific Antibody Format and the Organization of Immunological Synapses in T Cell-Redirecting Strategies for Cancer Immunotherapy

Cited by 9 publications

References 89 publications

Phase 1 clinical trial to assess safety and efficacy of NY-ESO-1-specific TCR T cells in HLA-A∗02:01 patients with advanced soft tissue sarcoma

Phase 1 clinical trial to assess safety and efficacy of NY-ESO-1-specific TCR T cells in HLA-A∗02:01 patients with advanced soft tissue sarcoma

Nucleolar protein TAAP1/C22orf46confers pro-survival signaling in non-small cell lung cancer

Therapeutic antibodies in oncology: an immunopharmacological overview

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