Combination Therapeutics with CAR-T Cell Therapy

Mohamad M. Adada, Elizabeth L. Siegler, Saad S. Kenderian

Research output: Chapter in Book/Report/Conference proceedingChapter


Adoptive cellular immunotherapy, specifically chimeric antigen receptor T-cell (CAR-T) therapy, has recently emerged as a breakthrough treatment for multiple hematological malignancies with potential for long term cure. However, multiple hurdles remain to be overcome. Some issues are inherent to CAR-T cells, such as suboptimal expansion, rapid exhaustion, or rejection. Other problems are related to the immunosuppressive tumor microenvironment, which dampens CAR-T activity. Additionally, CAR-T cell treatment is associated with significant toxicities relating to activation of the immune system, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Multiple strategies are currently underway to increase CAR-T efficacy and decrease toxicity. Some of those strategies involve creating optimized stand-alone CAR-T cell products, while other strategies involve combining existing CAR-T therapies with other treatment modalities. In this chapter, we will focus on combination strategies that are currently being used and/or are under exploration. We will first discuss strategies used to increase CAR-T effectiveness through combination with immunomodulatory agents, cancer-directed therapies, tumor antigen expression enhancers, or HCT. We will then discuss strategies aimed at decreasing CAR-T toxicity through combination with other immunomodulatory agents. All current clinical trials exploring these strategies will also be discussed.

Original languageEnglish (US)
Title of host publicationCancer Drug Discovery and Development
PublisherHumana Press Inc.
Number of pages22
StatePublished - 2022

Publication series

NameCancer Drug Discovery and Development
ISSN (Print)2196-9906
ISSN (Electronic)2196-9914


  • CAR-T combination therapy
  • Cellular immunotherapy
  • Chimeric antigen receptor T cells
  • Cytotoxic therapy
  • GM-CSF
  • Hematopoietic cell transplantation
  • Immunomodulation
  • Oncolytic viral therapy
  • Radiation
  • Solid tumors
  • Tocilizumab

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Cancer Research


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