Clinical CAR-T Cell and Oncolytic Virotherapy for Cancer Treatment

Watanabe, Norihiro; McKenna, Mary K.; Shaw, Amanda Rosewell; Suzuki, Masataka

doi:10.1016/j.ymthe.2020.10.023

Cited by 61 publications

(41 citation statements)

References 180 publications

(141 reference statements)

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“…Although lymphodepletion typically is also common in the clinic, an added potential benefit of systemically targeting PTP1B with MSI-1436 might be the alleviation of inhibitory constraints imposed on endogenous tumor-resident T cells, which might serve to prevent the emergence of antigen loss tumor variants during CAR T cell therapy (52). Similar outcomes have been sought when CAR T therapies have been combined with PD-1 blockade or oncolytic vaccines (43,52,53). Although further studies are required to explore such possibilities, targeting PTP1B with specific inhibitors stands to transform CAR T cell therapy and readily extend the utility of CAR T cells to the effective therapy of recalcitrant solid tumors.…”

Section: Discussionmentioning

confidence: 99%

PTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity

Wiede

et al. 2022

Cancer Discovery

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Immunotherapies aimed at alleviating the inhibitory constraints on T cells have revolutionized cancer management. To date, these have focused on the blockade of cell-surface checkpoints such as PD-1. Herein we identify protein tyrosine phosphatase 1B (PTP1B) as an intracellular checkpoint that is upregulated in T cells in tumors. We show that increased PTP1B limits T-cell expansion and cytotoxicity to contribute to tumor growth. T cell–specific PTP1B deletion increased STAT5 signaling, and this enhanced the antigen-induced expansion and cytotoxicity of CD8+ T cells to suppress tumor growth. The pharmacologic inhibition of PTP1B recapitulated the T cell–mediated repression of tumor growth and enhanced the response to PD-1 blockade. Furthermore, the deletion or inhibition of PTP1B enhanced the efficacy of adoptively transferred chimeric antigen receptor (CAR) T cells against solid tumors. Our findings identify PTP1B as an intracellular checkpoint whose inhibition can alleviate the inhibitory constraints on T cells and CAR T cells to combat cancer. Significance: Tumors subvert antitumor immunity by engaging checkpoints that promote T-cell exhaustion. Here we identify PTP1B as an intracellular checkpoint and therapeutic target. We show that PTP1B is upregulated in intratumoral T cells and that its deletion or inhibition enhances T-cell antitumor activity and increases CAR T-cell effectiveness against solid tumors. This article is highlighted in the In This Issue feature, p. 587

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Section: Discussionmentioning

confidence: 99%

PTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity

Wiede

et al. 2022

Cancer Discovery

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“…Oncolytic viruses (OVs) can not only selectively infect and lyse tumor cells [ 102 ], but they can also enhance tumor antigen presentation, stimulate their own immune response, and regulate the immunosuppressive microenvironment by inducing antiviral response, inflammatory response, and the production of cytokines (such as GM-CSF) [ 103 , 104 ]. CAR-T cell therapy combined with gene-modified OVs can significantly induce CAR-T cells to penetrate TME and improve their therapeutic effect in solid tumors [ 105 ]. In a mouse model of prostate cancer, Tanoue et al [ 106 ] used an “all-in-one” treatment whereby HER-2-targeted CAR-T cells were combined with an oncolytic adenovirus that specifically expressed PD-L1 antibodies.…”

Section: Prospects Of Car-t For the Treatment Of Prostate Cancermentioning

confidence: 99%

Prospect of Prostate Cancer Treatment: Armed CAR-T or Combination Therapy

Jiang

Wen

et al. 2022

Cancers

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The incidence rate of prostate cancer is higher in male cancers. With a hidden initiation of disease and long duration, prostate cancer seriously affects men’s physical and mental health. Prostate cancer is initially androgen-dependent, and endocrine therapy can achieve good results. However, after 18–24 months of endocrine therapy, most patients eventually develop castration-resistant prostate cancer (CRPC), which becomes metastatic castration resistant prostate cancer (mCRPC) that is difficult to treat. Chimeric Antigen Receptor T cell (CAR-T) therapy is an emerging immune cell therapy that brings hope to cancer patients. CAR-T has shown considerable advantages in the treatment of hematologic tumors. However, there are still obstacles to CAR-T treatment of solid tumors because the physical barrier and the tumor microenvironment inhibit the function of CAR-T cells. In this article, we review the progress of CAR-T therapy in the treatment of prostate cancer and discuss the prospects and challenges of armed CAR-T and combined treatment strategies. At present, there are still many obstacles in the treatment of prostate cancer with CAR-T, but when these obstacles are solved, CAR-T cells can become a favorable weapon for the treatment of prostate cancer.

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“…Although initially envisioned to act primarily via their tumoricidal actions, over the last decade oncolytic viruses have emerged as potent immune activators and promising partners for cancer immunotherapies. The potential and promising preclinical and clinical findings of combinations of OVs with major immunotherapeutic approaches such as immune checkpoint inhibitors, T cell therapies, and cancer vaccines are beyond the scope of this small molecule themed review but are extensively discussed in recent publications [ 22 , 229 , 230 , 231 , 232 , 233 ]. Small molecule compounds that augment the antitumor immune response can modulate the tumor microenvironment or affect the adaptive immunity arm.…”

Section: Combinations Improving the Antitumor Immune Responsementioning

confidence: 99%

Combining Oncolytic Viruses and Small Molecule Therapeutics: Mutual Benefits

Spiesschaert

Angerer

Park

et al. 2021

Cancers

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The focus of treating cancer with oncolytic viruses (OVs) has increasingly shifted towards achieving efficacy through the induction and augmentation of an antitumor immune response. However, innate antiviral responses can limit the activity of many OVs within the tumor and several immunosuppressive factors can hamper any subsequent antitumor immune responses. In recent decades, numerous small molecule compounds that either inhibit the immunosuppressive features of tumor cells or antagonize antiviral immunity have been developed and tested for. Here we comprehensively review small molecule compounds that can achieve therapeutic synergy with OVs. We also elaborate on the mechanisms by which these treatments elicit anti-tumor effects as monotherapies and how these complement OV treatment.

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Clinical CAR-T Cell and Oncolytic Virotherapy for Cancer Treatment

Cited by 61 publications

References 180 publications

PTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity

PTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity

Prospect of Prostate Cancer Treatment: Armed CAR-T or Combination Therapy

Combining Oncolytic Viruses and Small Molecule Therapeutics: Mutual Benefits

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