CD103 + cDC1 and endogenous CD8 + T cells are necessary for improved CD40L-overexpressing CAR T cell antitumor function

• Published in: Nature communications Vol. 11; no. 1; pp. 6171 - 10
• Main Authors: Kuhn, Nicholas F, Lopez, Andrea V, Li, Xinghuo, Cai, Winson, Daniyan, Anthony F, Brentjens, Renier J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 02.12.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adaptive Immunity; Animals; Anticancer properties; Antigen Presentation; Antigens; Antigens, CD - genetics; Antigens, CD - immunology; Antitumor activity; Basic-Leucine Zipper Transcription Factors - deficiency; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - immunology; CD103 antigen; CD11b antigen; CD11b Antigen - deficiency; CD11b Antigen - genetics; CD11b Antigen - immunology; CD40 Ligand - genetics; CD40 Ligand - immunology; CD40L protein; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell therapy; Chimeric antigen receptors; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Female; Gene Expression; Immune response; Immune system; Immunity; Immunity, Innate; Immunophenotyping; Immunotherapy; Immunotherapy, Adoptive - methods; Integrin alpha Chains - deficiency; Integrin alpha Chains - genetics; Integrin alpha Chains - immunology; Lymphocytes; Lymphocytes T; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - immunology; Lymphoma, B-Cell - pathology; Lymphoma, B-Cell - therapy; Memory cells; Mice; Mice, Inbred BALB C; Mice, Knockout; Neoplasm Transplantation; Optimization; Receptors; Receptors, Chimeric Antigen - genetics; Receptors, Chimeric Antigen - immunology; Repressor Proteins - deficiency; Repressor Proteins - genetics; Repressor Proteins - immunology

While effective in specific settings, adoptive chimeric antigen receptor (CAR) T cell therapy for cancer requires further improvement and optimization. Our previous results show that CD40L-overexpressing CAR T cells mobilize endogenous immune effectors, resulting in improved antitumor immunity. Howe...