Emerging Novel Combined CAR-T Cell Therapies

Nguyễn, Anh Tuấn; Johanning, Gary L.; Shi, Yihui

doi:10.3390/cancers14061403

Cited by 10 publications

(11 citation statements)

References 131 publications

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“…Induction of antibody-dependent cell cytotoxicity (ADCC) via the Fc-gamma receptor is another multi-target CAR T-cell approach that enables ADCC to CAR T-cells. Hence, by endowing CAR T-cells with ADCC activity via the Fc-gamma receptor IIIa (CD16), they exhibit sustained proliferation and cytotoxicity to antibody-targeted cancer cells ( 228 ). In CRC, CD16-CAR T-cells combined with cetuximab decreased the viability of KRAS-mutated HCT116 CRC cells in vitro , decreased tumor growth in a SCID mouse model, and increased disease-free survival ( 229 ).…”

Section: Discussionmentioning

confidence: 99%

“…Finally, combination therapies are being developed for improving immune response, minimizing on-target off-tumor toxicities, and transforming immunologically “cold” to “hot” tumors ( 230 ). A combination of CAR NK and CAR T-cells can harness the advantages of both CAR NK and CAR T-cells, allowing for both rapid and persistent killing while potentially minimizing the toxicities associated with CAR-T cells ( 228 , 231 – 233 ). The development of these therapies is poised to be the next frontier in immunotherapy as it will result in more robust immune attacks and effective clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

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CAR T-cells for colorectal cancer immunotherapy: Ready to go?

et al. 2022

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Chimeric antigen receptor (CAR) T-cells represent a new genetically engineered cell-based immunotherapy tool against cancer. The use of CAR T-cells has revolutionized the therapeutic approach for hematological malignancies. Unfortunately, there is a long way to go before this treatment can be developed for solid tumors, including colorectal cancer. CAR T-cell therapy for colorectal cancer is still in its early stages, and clinical data are scarce. Major limitations of this therapy include high toxicity, relapses, and an impermeable tumor microenvironment for CAR T-cell therapy in colorectal cancer. In this review, we summarize current knowledge, highlight challenges, and discuss perspectives regarding CAR T-cell therapy in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CAR T-cells for colorectal cancer immunotherapy: Ready to go?

et al. 2022

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“…Cancer cells often create the vascular system around the tumor to grow more rapidly. Since the expression of VEGF and VEGFR in tumors is related to their angiogenesis and metastasis ( 92 ), tumor vasculature has been a major target for CAR-T cells. The VEGFR2-NbCAR-T cells could efficiently lyse the VEGFR2 + tumor cells and produce IFN-γ and IL-2 cytokines ( 77 ).…”

Section: Nanobody-based T-cell Immunotherapymentioning

confidence: 99%

Nanobodies in cell-mediated immunotherapy: On the road to fight cancer

et al. 2023

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The immune system is essential in recognizing and eliminating tumor cells. The unique characteristics of the tumor microenvironment (TME), such as heterogeneity, reduced blood flow, hypoxia, and acidity, can reduce the efficacy of cell-mediated immunity. The primary goal of cancer immunotherapy is to modify the immune cells or the TME to enable the immune system to eliminate malignancies successfully. Nanobodies, known as single-domain antibodies, are light chain-free antibody fragments produced from Camelidae antibodies. The unique properties of nanobodies, including high stability, reduced immunogenicity, enhanced infiltration into the TME of solid tumors and facile genetic engineering have led to their promising application in cell-mediated immunotherapy. They can promote the cancer therapy either directly by bridging between tumor cells and immune cells and by targeting cancer cells using immune cell-bound nanobodies or indirectly by blocking the inhibitory ligands/receptors. The T-cell activation can be engaged through anti-CD3 and anti-4-1BB nanobodies in the bispecific (bispecific T-cell engagers (BiTEs)) and trispecific (trispecific T-cell engager (TriTEs)) manners. Also, nanobodies can be used as natural killer (NK) cell engagers (BiKEs, TriKEs, and TetraKEs) to create an immune synapse between the tumor and NK cells. Nanobodies can redirect immune cells to attack tumor cells through a chimeric antigen receptor (CAR) incorporating a nanobody against the target antigen. Various cancer antigens have been targeted by nanobody-based CAR-T and CAR-NK cells for treating both hematological and solid malignancies. They can also cause the continuation of immune surveillance against tumor cells by stopping inappropriate inhibition of immune checkpoints. Other roles of nanobodies in cell-mediated cancer immunotherapy include reprogramming macrophages to reduce metastasis and angiogenesis, as well as preventing the severe side effects occurring in cell-mediated immunotherapy. Here, we highlight the critical functions of various immune cells, including T cells, NK cells, and macrophages in the TME, and discuss newly developed immunotherapy methods based on the targeted manipulation of immune cells and TME with nanobodies.

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“… 46 , 47 These promising results in hematological malignancies have spurred a tidal wave of clinical trials on CAR‐T‐cell therapy (Table 1 ). 48 , 49 , 50 Due to further encouraging results in hematological malignancies, CAR‐T‐cell therapy was suggested for treatment of various solid tumors. However, the results of CAR‐T‐cell therapy in solid tumors were less efficient as compared to hematological malignancies.…”

Section: Car‐t‐ Cell Therapy For Hematological Malignanciesmentioning

confidence: 99%