Recently, the administrations of immune checkpoint modulators (represented by anti-CTLA4 and anti-PD antibodies) and adoptive immune cells (represented by CAR-T) have exhibited unexpected antitumor effect in multiple types of cancer, bringing a new era for cancer therapy.
Redirecting the recognition specificity of T lymphocytes to designated tumour cell surface antigens by transferring chimeric antigen receptor (CAR) genes is becoming an effective strategy to combat cancer.
<b>Purpose:</b> Chimeric Antigen Receptor T(CAR-T) cell therapy is an immunotherapy approach used in treating cancer which has seen rapid development over the decades.
The increasing use of multiple immunomodulatory (IMD) agents for cancer therapies (e.g. antibodies targeting immune checkpoints, bispecific antibodies, and chimeric antigen receptor [CAR]-T cells), is raising questions on their potential immunogenicity and effects on treatment.
Cancer immunotherapy has achieved remarkable clinical efficacy through recent advances such as chimeric antigen receptor-T cell (CAR-T) therapy, immune checkpoint blockade (ICB) therapy, and neoantigen vaccines.
In addition to CAR T-cell cytotoxicity, the αE-tag-specific T cells can be empowered with cancer-fighting ability in case of relapse, hence, have versatile utility.
Adoptive T cell therapy (ACT) is a safe and effective personalized cancer immunotherapy that can comprise naturally occurring ex vivo expanded cells (e.g., tumor-infiltrating lymphocytes [TIL]) or T cells genetically engineered to confer antigen specificity (T-cell receptor [TCR] or chimeric antigen receptor [CAR] engineered T cells) to mediate cancer rejection.
Given that multiple genetic alterations are the main factors that drive genesis and development of tumor, CRISPR-Cas9 system has been applied to correct cancer-causing gene mutations and deletions and to engineer immune cells, such as chimeric antigen receptor T (CAR T) cells, for cancer immunotherapeutic applications.
CAR -T cells or CAR- NK cells containing full length CS1 or the signaling domain of 2B4 with TCR-ζ have shown promising results to treat cancer and autoimmune diseases.
CAR-T therapy, grafting the specificity of a monoclonal antibody onto a T cell to target certain cancer cells, has been recognized as a promising therapeutic approach for cancer control as evidenced by the two CAR-T products proved by FDA in 2017.
Chimeric antigen receptor T (CAR-T) cells engineered with lentiviral and retroviral vectors have been successfully applied to treat patients with B cell malignancy.
The success of chimeric antigen receptor-modified T-cell (CAR-T) therapy for B-cell lymphocyte malignancies targeting CD19 places it in a rapidly growing field in cancer immunotherapy for both hematological and solid tumors.
Cancer immunotherapy has made unprecedented breakthrough in the fields of chimeric antigen receptor-redirected T (CAR T) cell therapy and immune modulation.
We also provide information of the future directions on how to enhance engineering the next smarter generations of CAR T cells in order to decrease the adverse effects and increase the potency and efficacy of CAR T cells against cancer.
In humanized mice with high leukemia burden, CAR T cell-mediated clearance of cancer triggered high fever and elevated IL-6 levels, which are hallmarks of CRS.
These studies identify a previously uncharacterized and ubiquitously expressed immunosuppressive ligand CD70 in GBMs that also holds potential for serving as a novel CAR target for cancer immunotherapy in gliomas.
Notable trends in the patent literature include both the development of combination therapies to combat the heterogeneous nature of GBM, and the use of immunotherapies building on the promise of cancer vaccines and CAR T-cell therapy.
Rapid development of new therapies targeting B-cell signaling and survival pathways and increased use of chimeric antigen receptor T-cell (CAR-T) therapy will likely result in more acquired deficiencies of humoral immunity and infections in persons with cancer.