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TARP as antigen in cancer immunotherapy.

ABSTRACT: In recent decades, immunotherapy has become a pivotal element in cancer treatment. A remaining challenge is the identification of cancer-associated antigens suitable as targets for immunotherapeutics with potent on-target and few off-tumor effects. The T-cell receptor gamma (TCRγ) chain alternate reading frame protein (TARP) was first discovered in the human prostate and androgen-sensitive prostate cancer. Thereafter, TARP was also identified in breast and endometrial cancers, salivary gland tumors, and pediatric and adult acute myeloid leukemia. Interestingly, TARP promotes tumor cell proliferation and migration, which is reflected in an association with worse survival. TARP expression in malignant cells, its role in oncogenesis, and its limited expression in normal tissues raised interest in its potential utility as a therapeutic target, and led to development of immunotherapeutic targeting strategies. In this review, we provide an overview of TARP expression, its role in different cancer types, and currently investigated TARP-directed immunotherapeutic options.

SUBMITTER: Vanhooren J

PROVIDER: S-EPMC8164403 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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TARP as antigen in cancer immunotherapy.

Vanhooren Jolien J Derpoorter Charlotte C Depreter Barbara B Deneweth Larissa L Philippé Jan J De Moerloose Barbara B Lammens Tim T

Cancer immunology, immunotherapy : CII 20210529 11

In recent decades, immunotherapy has become a pivotal element in cancer treatment. A remaining challenge is the identification of cancer-associated antigens suitable as targets for immunotherapeutics with potent on-target and few off-tumor effects. The T-cell receptor gamma (TCRγ) chain alternate reading frame protein (TARP) was first discovered in the human prostate and androgen-sensitive prostate cancer. Thereafter, TARP was also identified in breast and endometrial cancers, salivary gland tum ...[more]

PMID: 34050774

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Project description:BackgroundTumor antigen (TA)-targeted monoclonal antibody (mAb) immunotherapy can be effective for the treatment of a broad range of cancer etiologies; however, these approaches have demonstrated variable clinical efficacy for the treatment of patients with prostate cancer (PCa). An obstacle currently impeding translational progress has been the inability to quantify the mAb dose that reaches the tumor site and binds to the targeted TAs. The coupling of mAb to nanoparticle-based magnetic resonance imaging (MRI) probes should permit in vivo measurement of patient-specific biodistributions; these measurements could facilitate future development of novel dosimetry paradigms wherein mAb dose is titrated to optimize outcomes for individual patients.MethodsThe prostate stem cell antigen (PSCA) is broadly expressed on the surface of prostate cancer (PCa) cells. Anti-human PSCA monoclonal antibodies (mAb 7F5) were bound to Au/Fe(3)O(4) (GoldMag) nanoparticles (mAb 7F5@GoldMag) to serve as PSCA-specific theragnostic MRI probe permitting visualization of mAb biodistribution in vivo. First, the antibody immobilization efficiency of the GoldMag particles and the efficacy for PSCA-specific binding was assessed. Next, PC-3 (prostate cancer with PSCA over-expression) and SMMC-7721 (hepatoma cells without PSCA expression) tumor-bearing mice were injected with mAb 7F5@GoldMag for MRI. MRI probe biodistributions were assessed at increasing time intervals post-infusion; therapy response was evaluated with serial tumor volume measurements.ResultsTargeted binding of the mAb 7F5@GoldMag probes to PC-3 cells was verified using optical images and MRI; selective binding was not observed for SMMC-7721 tumors. The immunotherapeutic efficacy of the mAb 7F5@GoldMag in PC-3 tumor-bearing mice was verified with significant inhibition of tumor growth compared to untreated control animals.ConclusionOur promising results suggest the feasibility of using mAb 7F5@GoldMag probes as a novel paradigm for the detection and immunotherapeutic treatment of PCa. We optimistically anticipate that the approaches have the potential to be translated into the clinical settings.

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TARP as antigen in cancer immunotherapy.

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TARP as antigen in cancer immunotherapy.

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