Table 1 Therapeutic strategies to overcome T-cell depletion
From: Mechanisms of T-cell Depletion in Tumors and Advances in Clinical Research
Therapeutic Strategy | Mechanism | Advantages | Disadvantages | Clinical Applications/Examples |
|---|---|---|---|---|
CAR-T-cell Therapy | Genetic engineering of T cells to express CARs that specifically target tumor antigens. | - High specificity and potency against target cancer cells. - Proven efficacy in certain hematological malignancies. -Potential for long-term remission. | -Limited efficacy in solid tumors due to the tumor microenvironment - Risk of cytokine release syndrome and neurotoxicity. - Antigen escape leading to relapse. | - Successful treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma [67]. - Clinical trials targeting CCR9 in T-cell acute lymphoblastic leukemia [68]. - CAR-T therapy targeting carcinoembryonic antigen in colorectal cancer [69]. |
Tumor Vaccines | Stimulate the patient’s immune system to recognize and attack tumor-specific antigens. Types include tumor cell vaccines, protein/peptide vaccines, DNA/RNA vaccines, and viral vector vaccines. | -Can induce a specific and robust immune response. - Potential for long-lasting immunity. - Minimal toxicity compared to conventional therapies. | Challenges in achieving sufficient immune response. - Antigen escape and tumor heterogeneity. - Suppression by the tumor microenvironment. | - FDA-approved vaccines: Sipuleucel-T for metastatic castrate-resistant prostate cancer = [70], and T-VEC for unresectable melanoma [71]. - Clinical studies demonstrating prolonged overall survival with Sipuleucel-T [72]. |
Combination Therapy | Combining multiple therapeutic approaches, such as immune checkpoint inhibitors with CAR-T-cell therapy or tumor vaccines with immunometabolic modulators, to achieve synergistic effects. | -Enhanced efficacy through multiple mechanisms. - Potential to overcome resistance seen with single therapies. - Improved restoration of T-cell function and antitumor effects. | Increased complexity in treatment protocols. - Higher risk of compounded toxicities. - Potential for unpredictable interactions between therapies. | - Combination of T-VEC with immune checkpoint inhibitors showing improved response rates [73]. - Dual CAR-T-cell therapies targeting multiple antigens in multiple myeloma [74]. - PD-1 blocking antibodies combined with anti-complement C5a drugs in lung cancer models [75]. |