Olfactory receptor OR5V1 is an effective target for CAR T cells in ovarian cancer (207)

Martin, Alexandra; Galindo, Carmen Maria Anadon; Biswas, Subir; Mine, Jessica A.; Mandal, Gunjan; Innamarato, Patrick; Harro, Carly M.; Powers, John J.; Sprenger, Kimberly B.; Handley, Katelyn F.; Conejo-García, José R.

doi:10.1016/s0090-8258(22)01433-0

Cited by 1 publication

(5 citation statements)

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“…In 2022, Martin and colleagues reported that OR5V1 is expressed in a variety of ovarian cancer histological samples, while its expression in normal tissues is restricted to the testis ( 46 ). Owing to these findings, Martin et al.…”

Section: Target Antigens For Ovarian Cancer Car-t Therapymentioning

confidence: 99%

“…Owing to these findings, Martin et al. reported the development of an scFv-based 2 nd -generation CAR-T redirected against the OR5V1 antigen (OR5V1-redirected CAR-Ts) and eventually introduced this construct into human T cells via retroviral transduction ( 46 ). The results of the in vitro assays demonstrated that OR5V1-redirected CAR-Ts mediated specific tumoricidal effects against HeLa cells in a dose-dependent fashion while managing to spare a panel of normal human cells ( 46 ).…”

Section: Target Antigens For Ovarian Cancer Car-t Therapymentioning

confidence: 99%

“…reported the development of an scFv-based 2 nd -generation CAR-T redirected against the OR5V1 antigen (OR5V1-redirected CAR-Ts) and eventually introduced this construct into human T cells via retroviral transduction ( 46 ). The results of the in vitro assays demonstrated that OR5V1-redirected CAR-Ts mediated specific tumoricidal effects against HeLa cells in a dose-dependent fashion while managing to spare a panel of normal human cells ( 46 ). Moreover, Martin and colleagues established HeLa-bearing preclinical mouse models and reported that the treatment subjects experienced delayed tumor outgrowth under OR5V1-redirected CAR-T treatment ( 46 ).…”

Section: Target Antigens For Ovarian Cancer Car-t Therapymentioning

confidence: 99%

“…The results of the in vitro assays demonstrated that OR5V1-redirected CAR-Ts mediated specific tumoricidal effects against HeLa cells in a dose-dependent fashion while managing to spare a panel of normal human cells ( 46 ). Moreover, Martin and colleagues established HeLa-bearing preclinical mouse models and reported that the treatment subjects experienced delayed tumor outgrowth under OR5V1-redirected CAR-T treatment ( 46 ). Conclusively, these researchers demonstrated the antitumor potential of OR5V1-redirected CAR-T against OR5V1-positive malignancies with negligible toxicities ( 46 ).…”

Section: Target Antigens For Ovarian Cancer Car-t Therapymentioning

confidence: 99%

“…Moreover, Martin and colleagues established HeLa-bearing preclinical mouse models and reported that the treatment subjects experienced delayed tumor outgrowth under OR5V1-redirected CAR-T treatment ( 46 ). Conclusively, these researchers demonstrated the antitumor potential of OR5V1-redirected CAR-T against OR5V1-positive malignancies with negligible toxicities ( 46 ). To further elucidate the suitability of OR5V1 as an immunotherapy target antigen, in-depth preclinical and clinical assessments must be taken into consideration.…”

Section: Target Antigens For Ovarian Cancer Car-t Therapymentioning

confidence: 99%

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CAR-T cell immunotherapy for ovarian cancer: hushing the silent killer

Nasiri,

Farrokhi,

Safarzadeh Kozani

et al. 2023

Front. Immunol.

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As the most lethal gynecologic oncological indication, carcinoma of the ovary has been ranked as the 5th cause of cancer-related mortality in women, with a high percentage of the patients being diagnosed at late stages of the disease and a five-year survival of ~ 30%. Ovarian cancer patients conventionally undergo surgery for tumor removal followed by platinum- or taxane-based chemotherapy; however, a high percentage of patients experience tumor relapse. Cancer immunotherapy has been regarded as a silver lining in the treatment of patients with various immunological or oncological indications; however, mirvetuximab soravtansine (a folate receptor α-specific mAb) and bevacizumab (a VEGF-A-specific mAb) are the only immunotherapeutics approved for the treatment of ovarian cancer patients. Chimeric antigen receptor T-cell (CAR-T) therapy has achieved tremendous clinical success in the treatment of patients with certain B-cell lymphomas and leukemias, as well as multiple myeloma. In the context of solid tumors, CAR-T therapies face serious obstacles that limit their therapeutic benefit. Such hindrances include the immunosuppressive nature of solid tumors, impaired tumor infiltration, lack of qualified tumor-associated antigens, and compromised stimulation and persistence of CAR-Ts following administration. Over the past years, researchers have made arduous attempts to apply CAR-T therapy to ovarian cancer. In this review, we outline the principles of CAR-T therapy and then highlight its limitations in the context of solid tumors. Ultimately, we focus on preclinical and clinical findings achieved in CAR-T-mediated targeting of different ovarian cancer-associated target antigens.

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Section: Target Antigens For Ovarian Cancer Car-t Therapymentioning

confidence: 99%

Section: Target Antigens For Ovarian Cancer Car-t Therapymentioning

confidence: 99%