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.
In this chapter, we will highlight clinical application of CAR T cells in solid tumors, discuss hurdles that have impeded CAR T cell function in these malignancies, and propose methods to overcome these limitations.
<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.
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.
T cells armed with a chimeric antigen receptor, CAR T cells, have shown extraordinary activity against certain B lymphocyte malignancies, when targeted towards the CD19 B cell surface marker.
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.
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.
Cancer immunotherapy, including immune checkpoint blockade and adoptive CAR T-cell therapy, has clearly established itself as an important modality to treat melanoma and other malignancies.
Adoptive immunotherapy based on chimeric antigen receptor-modified T (CAR-T) cells has been demonstrated as one of the most promising therapeutic strategies in the treatment of malignancies.
While immunotherapy with chimeric antigen receptor T (CAR-T) cells has shown much promise in haematological malignancies, their efficacy for solid tumours is challenged by the lack of tumour-specific antigens required to avoid on-target, off-tumour effects.
Autologous T cells that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the B cell antigen CD19 have yielded remarkable clinical responses in patients with B cell malignancies, and are now on the market as anticancer 'drugs'.
Several prevention strategies such as predictive biomarkers of CRS and neurotoxicity and modified CAR-T with 'built-in' safety mechanisms are being studied, with the potential to greatly expand the safety and applicability of CAR-T treatment across various malignancies.
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.
Chimeric antigen receptor-modified T (CAR T) cells exhibit very effective function in elimination of relapsed/refractory B-cell lymphoid malignancies, we investigated their use in a patient with relapsed MCL.
More importantly, CAR T therapy had a higher CSER in patients with hematologic malignancies, and it had a similar RR in patients with different malignancies.
Chimeric antigen receptor T (CAR-T) cell therapy provides possibility for the treatment of malignancies since clinical trials have shown that CAR-T therapy has a significant anti-tumor effect.
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.
This landmark step brought CAR T-cell therapy to the commercial space and heralded a new era in managing refractory B-cell malignancies and FDA oversight of gene-modified therapies.See related article by O'Leary et al., p. 1142.
Adoptive cell therapy using CAR T cells has emerged as a novel treatment strategy with promising results against B cell malignancies; however, CAR T cells have not shown much success against solid malignancies.