CAR T Cell Therapy

https://meditropics.com/car-t-cell-therapy/

*Pratibha, **Sameer Gulati  

*Post Graduate resident , ** Professor

Department Of Medicine, Lady Hardinge Medical College, New Delhi 

Chimeric Antigen Receptor (CAR) T cell therapy revolutionizes cancer treatment by genetically engineering patients’ T cells to target tumor-specific antigens. CAR T cells exhibit remarkable precision in recognizing and eliminating cancer cells while sparing healthy tissues, offering a potent and personalized immunotherapeutic approach. Originating from pioneering research in the late 1980s, CAR T cell therapy has evolved through successive generations of CAR design, culminating in unprecedented clinical successes in hematological malignancies. With ongoing advancements and expanding clinical applications, CAR T cell therapy holds promise for transforming the oncology landscape and improving outcomes for patients with refractory or relapsed cancers.

In this comprehensive review, we aim to provide a thorough examination of the current state of CAR T cell therapy. We will delve into the intricacies of CAR T cell development, elucidate the underlying mechanisms of action, and explore the clinical applications across a spectrum of malignancies. Furthermore, we will discuss limitations confronting the field.

Development of CAR T Cell Therapy

The development of CAR T cells began with the pioneering work of Zelig Eshhar and colleagues in the late 1980s, who conceptualized the fusion of antigen recognition domains with T cell signaling molecules. Over subsequent decades, advances in molecular biology and cellular engineering have refined CAR design, leading to the creation of diverse CAR constructs targeting specific tumor antigens. This iterative process has seen the evolution of CAR T cells through multiple generations, each iteration fine-tuned to optimize tumor recognition, signaling, and persistence. Today, CAR T cell therapy represents a culmination of these efforts, offering a targeted and potent immunotherapeutic approach in cancer treatment.

MECHANISM OF ACTION

The mechanism of action of CAR T cell therapy involves a multi-step process aimed at specifically targeting and eliminating cancer cells. First, patients’ T cells are harvested and genetically modified to express chimeric antigen receptors (CARs) designed to recognize tumor-specific antigens. Upon infusion back into the patient, CAR T cells migrate to tumor sites guided by antigen recognition. Upon encountering tumor cells expressing the target antigen, CAR T cells engage with the tumor cell surface and initiate a cascade of signaling events, leading to T cell activation, proliferation, and release of cytotoxic molecules. This culminates in the destruction of tumor cells and subsequent activation of endogenous immune responses against residual cancer cells. Importantly, CAR T cells can persist in the body, providing long-term surveillance against cancer recurrence. Overall, the mechanism of action of CAR T cell therapy exploits the specificity and cytotoxic potential of engineered T cells to eradicate cancer while sparing healthy tissues.

CLINICAL IMPLICATIONS

The clinical implications of CAR T cell therapy are profound, offering a paradigm shift in cancer treatment. For patients with refractory or relapsed hematological malignancies, CAR T cell therapy represents a potential curative option, achieving high rates of complete remission and durable responses. Moreover, CAR T cell therapy holds promise for extending survival and improving quality of life in patients with advanced solid tumors. Despite challenges such as toxicity management and manufacturing constraints, the remarkable efficacy demonstrated in clinical trials underscores the transformative potential of CAR T cell therapy in reshaping the oncology landscape and offering new hope for patients with otherwise limited treatment options.

CHALLENGES FACED BY THE THERAPY

CAR T cell therapy, while promising, has notable disadvantages. It can induce severe toxicities like cytokine release syndrome (CRS) and neurotoxicity, necessitating intensive care management. Antigen escape variants may emerge, leading to treatment resistance. Manufacturing challenges, including scalability and cost, hinder widespread accessibility. Additionally, limited applicability to solid tumors due to heterogeneous antigen expression and off-target effects poses challenge.

 

REFERENCES

  1. Schuster, S. J., et al. (2017). Chimeric antigen receptor T cells in refractory B-cell lymphomas. New England Journal of Medicine, 377(26), 2545-2554.
  2. Park, J. H., et al. (2018). Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. New England Journal of Medicine, 378(5), 449-459.
  3. Neelapu, S. S., et al. (2017). Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. New England Journal of Medicine, 377(26), 2531-2544.
  4. June, C. H., et al. (2018). CAR T cell immunotherapy: Beyond B cell malignancies. Journal of Clinical Investigation, 128(10), 4407-4415.
  5. O’Rourke, D. M., et al. (2017)
  6. Neelapu et al. (2017), Lee et al. (2014), O’Rourke et al. (2017), Levine & Miskin (2018), Beatty & O’Hara (2016), Lamers et al. (2016)

 

.