Combined Adjuvant of Poly I:C Improves Antitumor Effects of CAR-T Cells
In conclusion, CAR-T treatment combined with intratumoral delivery of poly I:C resulted in synergistic antitumor activity. We thus provide a rationale to translate this immunotherapeutic strategy to solid tumors.
Introduction
Adoptive T cell immunotherapy has been demonstrated to be a new way to fight malignancies. In particular, T lymphocytes engineered to express chimeric antigen receptor (CAR) have shown great promise in treating hematological malignancies (1). CD19-targeted CAR-T cells have been approved by FDA to treat relapsed B cell acute lymphoblastic leukemia (B-ALL) and Diffuse Large B-cell lymphoma (DLBCL) (2, 3).
CAR-T therapy is also a novel approach to treat other malignant tumors. Currently, Glypian-3 (GPC3), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor2 (HER2), carcinoembryonic antigen (CEA), disialoganglioside 2 (GD2), mesothelin, prostate-specific membrane antigen (PSMA), and interleukin-13Ra2 (IL13Ra2) have been tested as targets of CAR-T cells in solid tumor. However, CAR-T therapy for solid tumors has not been as efficient as those targeting hematologic malignancies (4–7).
The reasons for the limited success of CAR T cells in solid tumor are being actively investigated, and are likely multifactorial. One major reason is the immunosuppressive microenvironment that may impede the function and persistence of CAR T cells. This includes the presence of regulatory T cells, tumor-associated macrophages, myeloi...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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