Manufacturing of CRISPR-edited primary mouse CAR T cells for cancer immunotherapy.

Editing chimeric antigen receptor (CAR) T cells by using CRISPR-Cas9 has become a routine strategy to improve their antitumor function or safety profile. Xenograft tumor models in immunodeficient mice are often used to evaluate the function of CRISPR-edited human CAR T cells. These models, however, lack functional immune systems and thus fail to recapitulate barriers such as the immunosuppressive tumor microenvironment (TME) that CAR T cells will encounter in patients.

CAR-T cell therapy and reconstructive oncologic surgery in peripheral solid tumors-A narrative review.

This review addresses the integration of chimeric antigen receptor (CAR)-T cell therapy with reconstructive oncologic surgery in treating peripheral solid tumors, including melanoma, sarcomas, breast cancer, and head and neck cancers. While CAR-T cells have demonstrated effectiveness in blood cancers, their efficacy in solid tumors has been limited due to tumor heterogeneity, immune suppression, and poor cellular infiltration. Emerging approaches involving localized CAR-T cell delivery, improved CAR design, and targeted antigen selection (such as HER2, MUC1, GD2, and B7-H3) are discussed as promising strategies to enhance therapeutic outcomes.

EZH1/EZH2 inhibition enhances adoptive T cell immunotherapy against multiple cancer models.

Tumor resistance to chimeric antigen receptor T cell (CAR-T) and, in general, to adoptive cell immunotherapies (ACTs) is a major challenge in the clinic. We hypothesized that inhibiting the tumor drivers' methyltransferases EZH2 and EZH1 could enhance ACT by rewiring cancer cells to a more immunogenic state. In human B cell lymphoma, EZH2 inhibition (tazemetostat) improved the efficacy of anti-CD19 CAR-T by enhancing activation, expansion, and tumor infiltration.

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies.

Shaping the Future of Myeloproliferative Neoplasm Therapy: Immune-Based Strategies and Targeted Innovations.

Numerous cutting-edge immunotherapy approaches have been developed for hematological malignancies, such as immune-checkpoint inhibitors for lymphomas, chimeric antigen receptor (CAR)-T-cell treatments for B-cell cancers, and monoclonal antibody therapies for acute myeloid leukemia (AML). However, achieving similar breakthroughs in MPNs has proven challenging. The key obstacles include the absence of universally expressed and MPN-specific surface markers, significant cellular and molecular variability among both individual patients and across different MPN subtypes, and the failure of treatments to stimulate an anti-tumor immune response due to the immune system disruptions caused by the myeloid neoplasm.