Why Should We Look Beyond Anti-CD 19 CAR-T Cells?
In the recent stem cell summit, we had so many strategies to improve the quality of stem cell transplants and make them successful. One of such strategies undertaken in the January Summit, held in Florida raises a concern over the performance of CD19 and finds pathways to improve its efficacy to target solid tumors.
The success of clinical studies on the efficacy of modified T cells garnered our hopes in the development of novel therapeutic treatments. We have witnessed that modification of chimeric antigen receptors (CARs) have been able to defy the cytotoxicity of tumors in many clinical studies. Engineered CD19 CAR-T cells being active in inducing anti-inflammatory immunity against B-cells malignancies, these cells are participating in the development of cancer adoptive immunotherapy.
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However, the hurdle in its way seems to be its ineffectiveness to combat solid tumors. We can find several factors that work against various approaches of these modified T-cells. The first one being the neoplasm activity of the microenvironment, which does not allow CAR-T cells to survive and reach the tumor surface. The host’s defensive mechanism becomes ineffective due to the useless anergic status developing from the ambiguous interactive communication amongst tumor components, stromal and immune cells.
Amidst these confusions, what pathways we should take to improve the performance of CD19 CAR-T cells? Or Should we look beyond some other immunotherapy to treat solid tumors?
Efficacy Of CD19 CAR-T Cells
Anti-tumor efficacy of anti CD19 CAR-T cells has been expressed in children and adults through many clinical studies. T-cells can express its anti-immunotherapy properties against a series of B-cell acute lymphoblastic leukemia and other B-cell malignancies. We have two anti-cancer immunotherapies infused with anti-CD19 CAR-T cells named YESCARTA and KYMRIAH. Both these drugs are useful in suppressing B-cell expressions.
While this antigen CD19 CAR-T cell is capable of treating many B-cell malignancies, it is ineffective to even target solid tumor cells. Why so?
Factors Behind CD19 CAR-T Cells Being Inefficient In Solid Tumor Control
Its poor efficacy against malignant epithelial cells is due to the lack of capacity to target specific antigens in the microenvironment. Its inability to target active splice variant of epidermal growth factor receptor (EGFR), causes the growth of solid tumors and creates a hostile nature for its survival.
Ways To Improve Antigen Anti-CD19 CAR-T Cell Performances
While this immunotherapy fails to provide a positive result for the patients with solid tumors, other antigens like anti GD-2 CAR-T cells have shown some promises to treat different malignant conditions in clinical trials. Therefore, we can demand more clinical trials which can bring forth the introduction of anti-cancer immunotherapy using antigens.
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By using IL-2 support and increasing the number of cells for the ACT in melanoma, we can achieve a positive result for patients with solid tumors. Simultaneously, the physical barriers created by epithelial and mesenchymal cells need to be restricted to prevent ill effects of the cytotoxic functions of the solid tumors. And to effectively increase its efficacy against solid tumors, its persistence, eruption in the environment and tumor homing should be increased.
At the same time, if this antigen underperforms despite some changes, we should look beyond this. A recent study showed that BCMA targeted CAR-T cells can effectively perform on tumor-specific cells to stop further spread of the diseases. Many clinical trials have shown promises that this antigen could provide adequate relief from multiple myeloma.
So, we can rest assured that clinical studies and research could bring us effective CAR-T cells based immunotherapy in order to combat multiple malignancies and myeloma in future.
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