Re-examination of MAGE-A3 as a T-cell Therapeutic Target

Martin, Aaron D.; Wang, Xueyin; Sandberg, Mark L.; Negri, Kathleen R; Wu, Mei; Warshaviak, Dora Toledo; Gabrelow, Grant B.; McElvain, Michele; Lee, Bella; Daris, Mark; Han, Xu; Kamb, Alexander

doi:10.1097/cji.0000000000000348

Cited by 21 publications

(23 citation statements)

References 31 publications

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“…Mass spectrometry experiments were conducted by Caprion Biosciences (Montreal, Canada) on human cell lines as previously described [15]. The mass spectrometry proteomics data will be deposited to the ProteomeXchange Consortium through the PRIDE partner repository.…”

Section: Mass Spectroscopic Analysis Of Peptidesmentioning

confidence: 99%

“…Jurkat NFAT activation functional assays were conducted as previously described [15,17]. Briefly, Jurkat cells were transfected with TCR or CAR constructs using standard protocols for the Neon™ transfection system (Invitrogen, MPK5000).…”

Section: Jurkat Nfat Functional Assaymentioning

confidence: 99%

“…Peripheral blood mononuclear cells (PBMCs) from healthy donors, obtained from AllCells (Alameda, California), were cultured and transduced with KRAS TCR or CAR constructs using custom lentivirus (Alstem) as previously described [15,17]. In the absence of enrichment, primary T cells were stained for TCR or CAR expression and pMHC probe binding similarly as described above for Jurkat cells.…”

Section: Primary T Cell Assaysmentioning

confidence: 99%

“…The capacity of mAbs to recognize not only single amino acid substitutions [12] but also specific pMHC determinants has long been appreciated [13,14]. To that end, recent library display methods have been used to identify mAbs and scFvs that bind pMHCs differentially based on single amino acid differences in the peptide portion of the target complex [15]. Vogelstein, Kinzler, Zhao and colleagues reported an A*11/KRAS/G12D mAb with good discrimination against wild type (WT [16]).…”

Section: Introductionmentioning

confidence: 99%

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Chimeric Antigen Receptors Directed at Mutant KRAS Exhibit an Inverse Relationship Between Functional Potency and Neoantigen Selectivity

Tokatlian

Asuelime

Naradikian

et al. 2022

Cancer Research Communications

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Neoantigens are among the most intriguing potential immuno-oncology targets because, unlike many cancer targets that are expressed on normal tissues, they are by definition restricted to cancer cells. Medicines directed at common neoantigens such as mutant KRAS are especially interesting because they may offer the convenience and cost of an off-the-shelf therapy. However, all common KRAS mutations produce proteins that differ from the wild type at a single amino acid, creating challenges for molecular discrimination. We have undertaken an effort to optimize scFvs against peptide/major histocompatibility antigen complexes composed of HLA-A*11 and either G12V or G12D mutant KRAS peptides. These scFvs could in principle be used in chimeric antigen receptor (CAR) T cell therapies for selected patients whose tumors bear either of these mutations. Here we show that optimization of such CARs involves a trade-off between potency and selectivity. We further show that targeting this family without high selectivity engenders risks of cross-reactivity against other members of the G-protein family to which KRAS belongs.

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Section: Mass Spectroscopic Analysis Of Peptidesmentioning

confidence: 99%

Section: Jurkat Nfat Functional Assaymentioning

confidence: 99%

Section: Primary T Cell Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Chimeric Antigen Receptors Directed at Mutant KRAS Exhibit an Inverse Relationship Between Functional Potency and Neoantigen Selectivity

Tokatlian

Asuelime

Naradikian

et al. 2022

Cancer Research Communications

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mentioning

confidence: 99%

Management of partial and non‐responding cutaneous squamous cell carcinoma

Jansen

Lodde

Griewank

et al. 2021

Acad Dermatol Venereol

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Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma are the most common types of skin cancer. For patients with locally advanced and metastatic cSCC, the programmed cell death 1 (PD‐1) inhibitor cemiplimab is approved for systemic treatment. Despite this revolutionary immunomodulatory therapeutic approach, tumours may fail to respond either completely or partially. In addition to the previously established local treatment with radiotherapy or systemic treatment with chemotherapy and epidermal growth factor receptor inhibitors, ongoing trials are currently focussed on re‐stimulating the antitumour immune response in patients with advanced cSCC refractory to PD‐1 inhibitors. In this review, ongoing and recently finished trials with different therapeutic approaches will be discussed.

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The role of CD4⁺ T cells in tumor and chronic viral immune responses

Xie,

Fang,

et al. 2023

MedComm

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Immunotherapies are mainly aimed to promote a CD8+ T cell response rather than a CD4+ T cell response as cytotoxic T lymphocytes (CTLs) can directly kill target cells. Recently, CD4+ T cells have received more attention due to their diverse roles in tumors and chronic viral infections. In antitumor and antichronic viral responses, CD4+ T cells relay help signals through dendritic cells to indirectly regulate CD8+ T cell response, interact with B cells or macrophages to indirectly modulate humoral immunity or macrophage polarization, and inhibit tumor blood vessel formation. Additionally, CD4+ T cells can also exhibit direct cytotoxicity toward target cells. However, regulatory T cells exhibit immunosuppression and CD4+ T cells become exhausted, which promote tumor progression and chronic viral persistence. Finally, we also outline immunotherapies based on CD4+ T cells, including adoptive cell transfer, vaccines, and immune checkpoint blockade. Overall, this review summarizes diverse roles of CD4+ T cells in the antitumor or protumor and chronic viral responses, and also highlights the immunotherapies based on CD4+ T cells, giving a better understanding of their roles in tumors and chronic viral infections.

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Re-examination of MAGE-A3 as a T-cell Therapeutic Target

Abstract: Supplemental Digital Content is available in the text.

Cited by 21 publications

References 31 publications

Chimeric Antigen Receptors Directed at Mutant KRAS Exhibit an Inverse Relationship Between Functional Potency and Neoantigen Selectivity

Chimeric Antigen Receptors Directed at Mutant KRAS Exhibit an Inverse Relationship Between Functional Potency and Neoantigen Selectivity

Management of partial and non‐responding cutaneous squamous cell carcinoma

The role of CD4⁺ T cells in tumor and chronic viral immune responses

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Re-examination of MAGE-A3 as a T-cell Therapeutic Target

Abstract: Supplemental Digital Content is available in the text.

Cited by 21 publications

References 31 publications

Chimeric Antigen Receptors Directed at Mutant KRAS Exhibit an Inverse Relationship Between Functional Potency and Neoantigen Selectivity

Chimeric Antigen Receptors Directed at Mutant KRAS Exhibit an Inverse Relationship Between Functional Potency and Neoantigen Selectivity

Management of partial and non‐responding cutaneous squamous cell carcinoma

The role of CD4+ T cells in tumor and chronic viral immune responses

Contact Info

Product

Resources

About

The role of CD4⁺ T cells in tumor and chronic viral immune responses