Recent Advances in CAR-Based Solid Tumor Immunotherapy

Abstract

Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design—such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells—have shown promising results in treating solid tumors, there are still challenges that need to be addressed. To overcome these limitations, other immune cells, such as natural killer (NK) cells and macrophages (M), have been developed as attractive options for efficient cancer immunotherapy of solid tumors. CAR-NK cells exhibit substantial clinical improvements with "off-the-shelf" availability and low toxicity. CAR-M cells have promising therapeutic potential because macrophages can infiltrate the TME of solid tumors. Here, we review the recent advances and future perspectives associated with engineered immune cell-based cancer immunotherapies for solid tumors. We also summarize ongoing clinical trials investigating the safety and efficacy of engineered immune cells, such as CAR-T, CAR-NK, and CAR-M, for targeting solid tumors.

Antitumor activities against breast cancers by an afucosylated anti‐HER2 monoclonal antibody H2Mab‐77‐mG2a‐f

“…The use of H 2 Mabs to create bispecific antibodies is another option for increasing anti‐HER2 treatment. Furthermore, attention has been drawn to chimeric antigen receptor‐T (CAR‐T) cell treatment, which possesses both antibody specificity and T cell cytotoxicity 81–83 . While the FDA authorized the first CD19 CAR‐T treatment for B‐cell lymphoma in 2017, no CAR‐T therapeutic targeting HER2 has yet to be produced 84 .…”

Antitumor Activities against Breast Cancers by an Afucosylated Anti-HER2 Monoclonal Antibody H₂Mab-77-mG_2a-f

“…The use of H2Mabs to create bispecific antibodies is another option for increasing anti-HER2 treatment. Furthermore, attention has been drawn to chimeric antigen receptor-T (CAR-T) cell treatment, which possesses both antibody specificity and T cell cytotoxicity [77][78][79]. While the FDA authorized the first CD19 CAR-T treatment for B-cell lymphoma in 2017, no CAR-T therapeutic targeting HER2 has yet to be produced [80].…”

CD155 and Its Receptors as Targets for Cancer Therapy

“…CARs usually contain an extracellular antibody-derived variable fragment (scFV) and an intracellular domain designed to drive activating signals, typically the intracellular domain of TCR/CD3 ζ-chain with the addition of co-stimulatory domains. This specific targeting boosts the ability of the T lymphocyte to kill tumor cells and has shown remarkable improvement of prognosis in several clinical trials, with the best results obtained in hematological malignancies [ 110 ]. Therefore, the development of new approaches improving this therapy in solid tumors is imperative.…”