Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 29, 2022

Abstract Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which called abscopal effect. The view RT as a simple treatment has dramatically changed in recent years, it now widely accepted that provoke immune response gives strong rationale the combination immunotherapy (iRT). Nevertheless, several points remain to be addressed such interaction system, identification best schedules with (IO), expansion mechanism amplify iRT. To answer these crucial questions, we roundly summarize underlying showing whole landscape clinical trials attempt identify In consideration rarity effect, propose occurrence induced by radiation promoted 100% molecular genetic level. Furthermore, “radscopal effect” refers using low-dose reprogram microenvironment may overcome resistance Taken together, could regarded trigger antitumor response, help IO used radical added into current standard regimen patients metastatic cancer.

Language: Английский

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Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(3), P. 772 - 784

Published: Jan. 18, 2024

Abstract There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 interleukin-15 (CAR19/IL-15) in 37 patients with CD19 + B malignancies. The primary objectives were safety efficacy, defined as day 30 overall response (OR). Secondary included 100 response, progression-free survival, survival CAR19/IL-15 NK persistence. No notable toxicities such cytokine release syndrome, neurotoxicity or graft-versus-host disease observed. OR rates 48.6% both. 1-year 68% 32%, respectively. Patients who achieved had higher levels longer persistence CAR-NK cells. Receiving from blood unit (CBU) nucleated red ≤ 8 × 10 7 collection-to-cryopreservation time 24 h was the most significant predictor superior outcome. these optimal CBUs highly functional enriched effector-related genes. In contrast, suboptimal upregulation inflammation, hypoxia cellular stress programs. Finally, using multiple mouse models, we confirmed antitumor activity CAR/IL-15 vivo. These findings uncover new features biology underscore importance donor selection therapies. ClinicalTrials.gov identifier: NCT03056339 .

Language: Английский

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Engineered TCR-T Cell Immunotherapy in Anticancer Precision Medicine: Pros and Cons

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: March 30, 2021

This review provides insight into the role of engineered T-cell receptors (TCRs) in immunotherapy. Novel approaches have been developed to boost anticancer immune system, including targeting new antigens, manufacturing or modified TCRs, and creating a safety switch for endo-suicide genes. In order re-activate T cells against tumors, immune-mobilizing monoclonal TCRs cancer (ImmTAC) as novel class manufactured molecules which are bispecific recognize both cells. The target special antigens such NY-ESO-1, AHNAK S2580F ERBB2 H473Y efficacy genetically is very important. Therefore, this discusses pros cons different approaches, ImmTAC, Herpes simplex virus thymidine kinase (HSV-TK), inducible caspase-9 Clinical trials related TCR-T cell therapy antibodies designed overcoming immunosuppression, recent advances made understanding how additionally examined. New that can better detect drive an effective response discussed well.

Language: Английский

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CAR-NK Cells in the Treatment of Solid Tumors

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5899 - 5899

Published: May 31, 2021

CAR-T (chimeric antigen receptor T) cells have emerged as a milestone in the treatment of patients with refractory B-cell neoplasms. However, despite having unprecedented efficacy against hematological malignancies, is far from flawless. Its greatest drawbacks arise challenging and expensive production process, strict patient eligibility criteria serious toxicity profile. One possible solution, supported by robust research, replacement T lymphocytes NK for CAR expression. seem to be an attractive vehicle expression they can derived multiple sources safely infused regardless donor–patient matching, which greatly reduces cost treatment. CAR-NK are known effective growing number preclinical findings indicate that activity non-hematological Here, we present thorough overview current state knowledge regarding use treating various solid tumors.

Language: Английский

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The Function of NK Cells in Tumor Metastasis and NK Cell-Based Immunotherapy

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2323 - 2323

Published: April 16, 2023

Metastatic tumors cause the most deaths in cancer patients. Treating metastasis remains primary goal of current research. Although immune system prevents and kills tumor cells, function metastatic has been unappreciated for decades because are able to develop complex signaling pathways suppress responses, leading them escape detection elimination. Studies showed NK cell-based therapies have many advantages promise fighting cancers. We here review progression, specifically focusing on ability cells antimetastasis, how cell attack, as well recent development effective antimetastatic immunotherapies.

Language: Английский

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Synapse-tuned CARs enhance immune cell anti-tumor activity

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(10), P. 1434 - 1445

Published: Feb. 2, 2023

Language: Английский

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Engineering the next generation of CAR-NK immunotherapies

International Journal of Hematology, Journal Year: 2021, Volume and Issue: 114(5), P. 554 - 571

Published: Aug. 28, 2021

Language: Английский

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Chimeric Antigen Receptor-Engineered Natural Killer (CAR NK) Cells in Cancer Treatment; Recent Advances and Future Prospects

Stem Cell Reviews and Reports, Journal Year: 2021, Volume and Issue: 17(6), P. 2081 - 2106

Published: Sept. 2, 2021

Language: Английский

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Preclinical and clinical studies of CAR-NK-cell therapies for malignancies

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 24, 2022

The development of chimeric antigen receptor T (CAR-T) cell therapy, a specific type immunotherapy, in recent decades was fantastic breakthrough for the treatment hematological malignancies. However, difficulties collecting normal cells from patients and time cost manufacturing CAR-T have limited application CAR-T-cell therapy. In addition, termination related clinical trials on universal therapy has made further research more difficult. Natural killer (NK) drawn great attention years. Chimeric receptor-NK (CAR-NK) is promising strategy malignant tumors because its lack potential causing graft-versus-host disease (GVHD). this review, we will address advances achievements CAR-NK

Language: Английский

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Targeting myeloid-derived suppressor cells to enhance natural killer cell-based immunotherapy

Pharmacology & Therapeutics, Journal Year: 2022, Volume and Issue: 235, P. 108114 - 108114

Published: Feb. 2, 2022

Myeloid-derived suppressor cells (MDSCs) are immune of the myeloid lineage that progressively accumulate in tumors and play an important role promoting tumor growth. MDSCs interact with other present microenvironment (TME) utilize multiple mechanisms to promote immunosuppression. On hand, natural killer (NK) cytotoxic innate system work as one first lines defense against tumors. However, regulating or suppressing NK within TME is poorly understood. This review discusses MDSC-associated immunosuppression, communication between microenvironment, how MDSC may impact NK-cell-based immunotherapies. We also explore various strategies increase cell cytotoxicity by blocking MDSC-mediated immunosuppression goal enhancing based anti-cancer therapeutics.

Language: Английский

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