bims-limsir 2022-09-11 papers

Issue of 2022‒09‒11
three papers selected by
Ivan V. Chernikov
Institute of Сhemical Biology and Fundamental Medicine of the SB RAS

Blood Lymphat Cancer. 2022 ;12 119-136

CAR T-Cell Therapy for Patients with Multiple Myeloma: Current Evidence and Challenges.

Matthew J Rendo, Jacinth J Joseph, Liem Minh Phan, Christin B DeStefano.

The therapeutic landscape of multiple myeloma (MM) has benefited from an emergence of novel therapies over the last decade. By inducing T-cell kill of target cancer cells, chimeric antigen receptor (CAR) T-cell therapies have improved outcomes of patients with hematologic malignancies. B-cell maturation antigen (BCMA) is the current target antigen of choice for most CAR T-cell products under investigation for MM. However, their shortcomings deal with logistical and clinical challenges, including limited availability, manufacturing times, and toxicities. This article provides an overview of recently developed and investigational CAR T-cell therapies for MM, highlighting current evidence and challenges.

Keywords: CAR T-cell; immunotherapy; multiple myeloma

DOI: https://doi.org/10.2147/BLCTT.S327016

Investig Clin Urol. 2022 Sep;63(5): 486-498

Current and future perspectives on CAR-T cell therapy for renal cell carcinoma: A comprehensive review.

Tae Jin Kim, Young Hwa Lee, Kyo Chul Koo.

In the clinical setting of renal cell carcinoma (RCC), immune reactions such as tumor-specific T cell responses can be spontaneous events or can be elicited by checkpoint inhibitors, cytokines, and other immunotherapy modalities. The results from immunotherapy have led to significant advances in treatment methods and patient outcomes. The approval of nivolumab primarily as a second-line monotherapy and the latest approval of novel combination therapies as first-line treatment have established the significance of immunotherapy in the treatment of RCC. In this perspective, chimeric antigen receptor (CAR)-T cell therapy represents a major advance in the developing field of immunotherapy. This treatment modality facilitates T cells to express specific CARs on the cell surface which are reinfused to the patient to treat the analogous tumor cells. After showing treatment potential in hematological malignancies, this new therapeutic approach has become a strong candidate as a therapeutic modality for solid neoplasms. Although CAR-T cell therapy has shown promise and clinical benefit compared to previous T-cell modulated immunotherapies, further studies are warranted to overcome unfavorable physiological settings and hindrances such as the lack of specific molecular targets, depletion of CAR-T cells, a hostile tumor microenvironment, and on/off-tumor toxicities. Several approaches are being considered and research is ongoing to overcome these problems. In this comprehensive review, we provide the rationale and preliminary results of CAR-T cell therapy in RCC and discuss emerging novel strategies and future directions.

Keywords: Immunotherapy; Metastasis; Receptors, chimeric antigen; Renal cell carcinoma; T cells

DOI: https://doi.org/10.4111/icu.20220103

Front Immunol. 2022 ;13 965224

Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma.

Encouraging response has been achieved in relapsed/refractory (R/R) B-cell lymphoma treated by chimeric antigen receptor T (CAR-T) cells. The efficacy and safety of CAR-T cells in central nervous system lymphoma (CNSL) are still elusive. Here, we retrospectively analyzed 15 patients with R/R secondary CNSL receiving CD19-specific CAR-T cell-based therapy. The patients were infused with CD19, CD19/CD20 or CD19/CD22 CAR-T cells following a conditioning regimen of cyclophosphamide and fludarabine. The overall response rate was 73.3% (11/15), including 9 (60%) with complete remission (CR) and 2 (13.3%) with partial remission (PR). During a median follow-up of 12 months, the median progression-free survival (PFS) was 4 months, and the median overall survival (OS) was 9 months. Of 12 patients with systemic tumor infiltration, 7 (58.3%) achieved CR in CNS, and 5 (41.7%) achieved CR both systemically and in CNS. Median DOR for CNS and systemic disease were 8 and 4 months, respectively. At the end point of observation, of the 7 patients achieved CNS disease CR, one was still alive with sustained CR of CNS disease and systemic disease. The other 6 died of systemic progression. Of the 15 patients, 11 (73.3%) experienced grades 1-2 CRS, and no patient had grades 3-4 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 (20%) patients, including 1 (6.6%) with grade 4 ICANS. All the CRS or ICANS were manageable. The CD19-specific CAR-T cell-based therapy appeared to be a promising therapeutic approach in secondary CNSL, based on its antitumor effects and an acceptable side effect profile, meanwhile more strategies are needed to maintain the response.

Keywords: chimeric antigen receptor t cell; immune effector cell-associated neurotoxicity syndrome; immunotherapy; relapsed/refractory; secondary central nervous system lymphoma

DOI: https://doi.org/10.3389/fimmu.2022.965224