T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors

Tsimberidou, Apostolia M.; Morris, Karlyle Van; Vo, Henry Hiep; Eck, Stephen L.; Lin, Yu Feng; Rivas, Jorge M.; Andersson, Börje S.

doi:10.1186/s13045-021-01115-0

Cited by 98 publications

(80 citation statements)

References 155 publications

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“…Among the limitations of engineered TCR are the restriction of this treatment to patients with a specific HLA subtype and, on the other hand the potential mechanisms of resistance such as loss of antigen, HLA or interferon gamma signaling ( 87 , 90 ).…”

Section: Vaccines and Adoptive Cell Therapymentioning

confidence: 99%

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Targeting KRAS in Non-Small Cell Lung Cancer

et al. 2022

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Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is the most frequently altered oncogene in Non-Small Cell Lung Cancer (NSCLC). KRAS mutant tumors constitute a heterogeneous group of diseases, different from other oncogene-derived tumors in terms of biology and response to treatment, which hinders the development of effective drugs against KRAS. Therefore, for decades, despite enormous efforts invested in the development of drugs aimed at inhibiting KRAS or its signaling pathways, KRAS was considered to be undruggable. Recently, the discovery of a new pocket under the effector binding switch II region of KRAS G12C has allowed the development of direct KRAS inhibitors such as sotorasib, the first FDA-approved drug targeting KRAS G12C, or adagrasib, initiating a new exciting era. However, treatment with targeted KRAS G12C inhibitors also leads to resistance, and understanding the possible mechanisms of resistance and which drugs could be useful to overcome it is key. Among others, KRAS G12C (ON) tricomplex inhibitors and different combination therapy strategies are being analyzed in clinical trials. Another area of interest is the potential role of co-mutations in treatment selection, particularly immunotherapy. The best first-line strategy remains to be determined and, due to the heterogeneity of KRAS, is likely to be based on combination therapies.

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Section: Vaccines and Adoptive Cell Therapymentioning

confidence: 99%

“…However, the intracellular nature of KRAS makes direct antigen binding difficult. Specific driver mutations in NSCLC may be associated with high levels of expression of multiple tumor surface antigens potentially amenable to targeting CAR-T and BiTE strategies ( 90 ).…”

Section: Vaccines and Adoptive Cell Therapymentioning

confidence: 99%

Targeting KRAS in Non-Small Cell Lung Cancer

et al. 2022

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“…These include, for instance, T cell receptor (TCR) gene therapy and cancer vaccines. TCR gene therapy involves the exploitation of a TCR that recognizes a specific HLA/peptide complex and which is transduced into a patient's own T cells [101]. Once administered, these modified T cells should elicit a robust antitumor immune response when the target antigen is expressed by cancer cells.…”

Section: Response To Other Immunotherapeutic Agentsmentioning

confidence: 99%

Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger?

et al. 2021

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Sarcomas comprise a collection of highly heterogeneous malignancies that can be grossly grouped in the categories of sarcomas with simple or complex genomes. Since the outcome for most sarcoma patients has barely improved in the last decades, there is an urgent need for improved therapies. Immunotherapy, and especially T cell checkpoint blockade, has recently been a game-changer in cancer therapy as it produced significant and durable treatment responses in several cancer types. Currently, only a small fraction of sarcoma patients benefit from immunotherapy, supposedly due to a general lack of somatically mutated antigens (neoantigens) and spontaneous T cell immunity in most cancers. However, genomic events resulting from chromosomal instability are frequent in sarcomas with complex genomes and could drive immunity in those tumors. Improving our understanding of the mechanisms that shape the immune landscape of sarcomas will be crucial to overcoming the current challenges of sarcoma immunotherapy. This review focuses on what is currently known about the tumor microenvironment in sarcomas and how this relates to their genomic features. Moreover, we discuss novel therapeutic strategies that leverage the tumor microenvironment to increase the clinical efficacy of immunotherapy, and which could provide new avenues for the treatment of sarcomas.

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“…Then, tumor-infiltrating lymphocytes (TILs) are amplified or engineered in vitro , and subsequently infused back into the patient to achieve precise cytotoxicity on tumor cells expressing the targeting antigens. ACT therapy involves the use of unmodified TILs, T cells with engineered T-cell receptor (TCR) fragments (TCR-Ts) [ 8 , 9 ], and chimeric antibody receptor-engineered T cells (CAR-Ts) [ 10 – 15 ]. The clinical outcome of both ICI and ACT treatments depends on the presence of tumor-derived antigens, which are the core of tumor immunotherapy in killing tumor cells by T lymphocytes [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting neoantigens for cancer immunotherapy

Zhao

Pan²,

Wang³

et al. 2021

Biomark Res

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Neoantigens, a type of tumor-specific antigens derived from non-synonymous mutations, have recently been characterized as attractive targets for cancer immunotherapy. Owing to the development of next-generation sequencing and utilization of machine-learning algorithms, it has become feasible to computationally predict neoantigens by depicting genetic alterations, aberrant post-transcriptional mRNA processing and abnormal mRNA translation events within tumor tissues. Consequently, neoantigen-based therapies such as cancer vaccines have been widely tested in clinical trials and have demonstrated promising safety and efficacy, opening a new era for cancer immunotherapy. We systematically summarize recent advances in the identification of both personalized and public neoantigens, neoantigen formulations and neoantigen-based clinical trials in this review. Moreover, we discuss future techniques and strategies for neoantigen-based cancer treatment either as a monotherapy or as a combination therapy with radiotherapy, chemotherapy or immune checkpoint inhibitors.

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T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors

Cited by 98 publications

References 155 publications

Targeting KRAS in Non-Small Cell Lung Cancer

Targeting KRAS in Non-Small Cell Lung Cancer

Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger?

Targeting neoantigens for cancer immunotherapy

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