ALKemy to enhance chimeric antigen receptor T cell immunotherapy for neuroblastoma.

in Cancer cell by Marco Ruella

TLDR

  • Researchers discovered that using ALK inhibitors can enhance the function of ALK-specific CAR T cells against neuroblastoma by increasing target density in cancer cells.
  • The combination of ALK inhibitors and ALK-specific CAR T cells showed promise in killing cancer cells and prolonging survival in animal models.
  • This finding could lead to new treatments for neuroblastoma and potentially other solid tumors that are hard to treat with CAR T cells.

Abstract

Chimeric antigen receptor (CAR) T cell immunotherapy in solid cancer is severely limited by the absence of ideal targets. In this issue of Cancer Cell, Bergaggio et al. find that anaplastic lymphoma kinase (ALK) inhibitors can enhance the function of ALK-specific CAR T cells against neuroblastoma by increasing target density in cancer cells.

Overview

  • The study aimed to explore the potential of anaplastic lymphoma kinase (ALK) inhibitors in enhancing the function of ALK-specific chimeric antigen receptor (CAR) T cells against neuroblastoma.
  • The researchers used ALK-specific CAR T cells and analyzed their function in the presence of ALK inhibitors in neuroblastoma cells.
  • The primary objective of the study was to investigate whether ALK inhibitors could increase target density in cancer cells, thereby enhancing the efficacy of ALK-specific CAR T cells.

Comparative Analysis & Findings

  • The study found that ALK inhibitors increased the density of ALK on the surface of neuroblastoma cells, making them more susceptible to attack by ALK-specific CAR T cells.
  • The researchers observed that the combination of ALK inhibitors and ALK-specific CAR T cells resulted in enhanced in vitro cytotoxicity and proliferation of CAR T cells against neuroblastoma cells.
  • The study also demonstrated that ALK inhibitors prolonged the survival of mice with established neuroblastoma tumors when combined with ALK-specific CAR T cells.

Implications and Future Directions

  • The findings suggest that ALK inhibitors may be used as a means to increase target density in cancer cells, thereby enhancing the efficacy of CAR T cell immunotherapy against solid tumors like neuroblastoma.
  • Future studies should investigate the optimal dosing and scheduling of ALK inhibitors for combination with CAR T cell therapy.
  • The study also highlights the need for further research into the mechanisms underlying the increased target density caused by ALK inhibitors and its implications for cancer immunotherapy.
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