bims-limsir 2023-08-13 papers

on Lipophilic modified siRNAs

Issue of 2023–08–13
two papers selected by
Ivan V. Chernikov, Institute of Сhemical Biology and Fundamental Medicine of the SB RAS

CAR-T cell therapy in hematological malignancies: Where are we now and where are we heading for?
Next-generation chimeric antigen receptors for T- and natural killer-cell therapies against cancer.

Eur J Haematol. 2023 Aug 07.

CAR-T cell therapy in hematological malignancies: Where are we now and where are we heading for?

Aalia N Khan, Sweety Asija, Juber Pendhari, Rahul Purwar.

  Chimeric antigen receptor T (CAR-T) therapy has emerged as a revolutionary new pillar in cancer care, particularly in relapsed/refractory (r/r) B-cell malignancies. Following impressive clinical outcomes in hematological malignancies, the FDA-approved six CAR-T cell products for indications such as lymphoma, leukemia, and myeloma. Despite the numerous advantages of CAR-T cell treatment, several challenges exist that interfere with its therapeutic efficacy. Serious adverse effects connected with the treatment continue to be a major concern. In addition, poor persistence of therapeutics and antigen escape frequently result in tumor relapse. Exorbitant treatment cost further remains a significant barrier to its effective implementation, limiting its accessibility. This review presents progress of CAR-T research, the key obstacles that hamper promising outcomes for patients with hematological malignancies, and a few strategies to overcome them.

Keywords:  CAR-T therapy; adverse events; efficacy; exorbitant cost; hematological malignancies; mitigation strategies; tumor relapse

DOI:  https://doi.org/10.1111/ejh.14076
Immunol Rev. 2023 Aug 07.

Next-generation chimeric antigen receptors for T- and natural killer-cell therapies against cancer.

Ye Li, Katayoun Rezvani, Hind Rafei.

  Adoptive cellular therapy using chimeric antigen receptor (CAR) T cells has led to a paradigm shift in the treatment of various hematologic malignancies. However, the broad application of this approach for myeloid malignancies and solid cancers has been limited by the paucity and heterogeneity of target antigen expression, and lack of bona fide tumor-specific antigens that can be targeted without cross-reactivity against normal tissues. This may lead to unwanted on-target off-tumor toxicities that could undermine the desired antitumor effect. Recent advances in synthetic biology and genetic engineering have enabled reprogramming of immune effector cells to enhance their selectivity toward tumors, thus mitigating on-target off-tumor adverse effects. In this review, we outline the current strategies being explored to improve CAR selectivity toward tumor cells with a focus on natural killer (NK) cells, and the progress made in translating these strategies to the clinic.

Keywords:  T cells; antitumor immunotherapy; chimeric antigen receptor (CAR); natural killer (NK) cells; synthetic immune cell engineering

DOI:  https://doi.org/10.1111/imr.13255