Here we demonstrate an approach to enhancing CAR-T function in solid tumors by directly vaccine-boosting donor cells through their chimeric receptor in vivo.
CD56-CAR-T cell therapy is a safe and effective approach and may be an option for children with solid tumors who are nonresponsive to conventional radiotherapy and chemotherapy, or are unsuitable for hematopoietic stem cell transplantation.
TME includes Tumor-Associated Stroma, Immunosuppressive cells and cytokines, tumor hypoxia and metabolism, and Immune Inhibitory Checkpoints which affect the CAR T cell efficacy and activity in solid tumors.
In this landscape, most studies have primarily focused on improving CAR-T cells and overcoming the unfavorable effects of tumor microenvironment on solid tumors.
These works confirmed that simultaneous use of cytokines, for example, rhIL-12, can increase the anti-tumor activity of CAR-T cells, especially for treatments of several types of solid tumors.
Although CAR-T cell therapy did not have satisfactory responses in solid tumors, researchers were still holding an optimistic attitude towards its future efficacy with more modifications of its structure.
Although CAR T cell therapy mediates robust responses in patients with hematological malignancies, this approach has been less effective for treating patients with solid tumors.
The anti-VEGFR2 CAR but not mock T cells mediated specific lysis of 293-KDR cells expressing human VEGFR2 and might be considered as a candidate for adoptive T-cell immunotherapy of solid tumors.
The data confirmed the antitumor ability and safety of CAR-T cells targeting EpCAM and may provide a new target for CAR-T cell therapies in treating solid tumors.
Here, we provide our perspective on how to improve the success of CAR T therapy in solid tumors by focusing on the aspects of target selection and the related TME in CAR T cell design, especially stressing the interplay between them.
Innovative approaches such as haploidentical stem cell transplantation, new monoclonal antibodies and immunotherapies as well as Chimeric Antigen Receptor T-cell (CAR-T cell) therapies are on the way as promising treatment options especially for patients with refractory hematologic malignancies and even in solid tumors.
There are obvious differences between the two countries in CAR-targeted antigens in solid tumors and genetic modifications besides CARs for enhancing the potency of CAR T-cells.