Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T

Abstract

In recent decades, immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy are two milestone achievements in clinical immunotherapy. However, both show limited efficacies in most solid neoplasms, which necessitates the exploration of new immunotherapeutic modalities. The failure of CAR-T and immune checkpoint blockade in several solid neoplasms is attributed to multiple factors, including low antigenicity of tumor cells, low infiltration of effector T cells, and diverse mechanisms of immunosuppression in the tumor microenvironment. New adoptive cell therapies have been attempted for solid neoplasms, including TCR-T, CAR-natural killer cells (CAR-NK), and CAR-macrophages (CAR-M). Compared to CAR-T, these new adoptive cell therapies have certain advantages in treating solid neoplasms. In this review, we summarized the 40-year evolution of adoptive cell therapies, then focused on the advances of TCR-T, CAR-NK, and CAR-M in solid neoplasms and discussed their potential clinical applications.

Four Ounces Can Move a Thousand Pounds: The Enormous Value of Nanomaterials in Tumor Immunotherapy

“…Its promotion of IL‐6 secretion by BMDCs was 9.4‐fold higher than in the CpG group and 79‐fold higher than in the PEI treatment group. In in vivo experiments, the researchers used the CpG@PEI complex on B16F10 tumor models in C57BL/6 mice, resulting in an average tumor volume of ≈300 mm [ 3 ] in this group, much smaller than that of the PEI and free CpG groups. Twelve days after vaccination with B16F10 tumor cells, the average tumor volume in the latter two groups reached over 900 mm [ 3 ] (Figure 2D, 2E).…”

“…In in vivo experiments, the researchers used the CpG@PEI complex on B16F10 tumor models in C57BL/6 mice, resulting in an average tumor volume of ≈300 mm [ 3 ] in this group, much smaller than that of the PEI and free CpG groups. Twelve days after vaccination with B16F10 tumor cells, the average tumor volume in the latter two groups reached over 900 mm [ 3 ] (Figure 2D, 2E). These experiments demonstrate that the complex effectively inhibits B16F10 melanoma by activating the body's immune system.…”

“…[ 1,2 ] However, the emergence of molecular sequencing and immunology techniques has shed new light on the role of the immune system in tumor progression. [ 3–5 ] Studies have demonstrated that tumors can evade the immune system by taming it, thereby enlisting it as a crucial ally in their survival and proliferation. Interestingly, while immunotherapy was pioneered by William Coley more than a century ago, it was limited by the cumbersome preparation process, inadequate documentation, and limitations of the time.…”

Personalised neoantigen‐based therapy in colorectal cancer

“…154 The sources of tumour antigens mainly include TAA and TSA. 155,156 TAA, such as CEA, is not an optimal target for immunotherapy. First, because TAA is also expressed in some normal tissues, immunotherapy against TAA may activate the immune response in non-target tissues and cause severe autoimmune toxicity, such as severe hepatitis, colitis, rapid respiratory failure, renal insufficiency and even death.…”

“…The sources of tumour antigens mainly include TAA and TSA 155,156 . TAA, such as CEA, is not an optimal target for immunotherapy.…”