The Ways of Isolating Neoantigen-Specific T Cells

Ding, Zhenyu

doi:10.3389/fonc.2020.01347

Cited by 26 publications

(17 citation statements)

References 86 publications

(119 reference statements)

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“…A fundamental challenge for the neoantigen approach is to effectively identify and isolate neoantigen-specific T cells or their TCRs, although several new strategies have been proposed. 145 A new approach included the co-culture of TILs with tandem minigene (TMG)-transfected or peptide-pulsed autologous APCs, and the single-cell RNA sequencing analysis of T cells to identify paired TCR sequences associated with cells expressing high levels of IFN-γ and IL-2 was reported. 146 Using high-throughput immunologic screening of mutant gene products identified via whole-exome sequencing was also reported for common gastrointestinal cancers.…”

Section: Methods To Enhance Til Therapymentioning

confidence: 99%

Prognostic and therapeutic TILs of cervical cancer—Current advances and future perspectives

Tang

Zhang²,

Chen³

et al. 2021

Molecular Therapy - Oncolytics

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Cervical cancer is a top lethal cancer for women worldwide. Although screening and vaccination programs are available in many countries, resulting in the decline of new cases, this is not true for developing countries where there are many new cases and related deaths. Cancer immunotherapy through adaptive cell therapy (ACT) has been applied in clinics, but now much attention is focused on autogenic tumor-infiltrating lymphocyte (TIL)-based therapy, which has shown more specificity and better ability to inhibit tumor growth. Data from melanoma and cervical cancers confirm that tumor-specific T cells in TILs can be expanded for more specific and effective ACT. Moreover, TILs are derived from individual patients and are ready to home back to kill tumor cells after patient infusion, aligning well with personalized and precision medicine. In addition to therapy, TIL cell types and numbers are good indicators of host immune response to the tumor, and thus they have significant values in prognosis. Because of the special relationship with human papillomavirus (HPV) infection, cervical cancer has some specialties in TIL-based prognosis and therapy. In this review, we summarize the recent advances in the prognostic significance of TILs and TIL-based therapy for cervical cancer and discuss related perspectives.

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Section: Methods To Enhance Til Therapymentioning

confidence: 99%

Prognostic and therapeutic TILs of cervical cancer—Current advances and future perspectives

Tang

Zhang²,

Chen³

et al. 2021

Molecular Therapy - Oncolytics

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show abstract

“…Treatment using our CAER could induce ICD and lead to the release of a higher amount of endogenous neoantigens, thereby enhancing tumor immunogenicity and triggering systemic immune responses without the need for sequencing to identify mutant neoantigen sequences. These advantages render our method more convenient than some of those previously reported (40,41). Furthermore, combining our regimen with other immunomodulators is expected to further improve its efficacy.…”

Section: Discussionmentioning

confidence: 91%

A Local and Low-Dose Chemotherapy/Autophagy-Enhancing Regimen Treatment Markedly Inhibited the Growth of Established Solid Tumors Through a Systemic Antitumor Immune Response

Yuan

et al. 2021

Front. Oncol.

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Chemotherapy is one of the main options for the treatment of a variety of malignant tumors. However, the severe side effects resulting from the killing of normal proliferating cells limit the application of cancer-targeting chemotherapeutic drugs. To improve the efficacy of classic systemic chemotherapy, the local delivery of high-dose chemotherapeutic drugs was developed as a method to enhance local drug concentrations and minimize systemic toxicity. Studies have demonstrated that chemotherapy is often accompanied by cancer-associated immunogenic cell death (ICD) and that autophagy is involved in the induction of ICD. To improve the efficacy of local cancer chemotherapy, we hypothesized that the local delivery of chemotherapeutic plus autophagy-enhancing agents would enhance the promotive effects of ICD on the antitumor immune response. Here, we report that a low-dose chemotherapy/autophagy enhancing regimen (CAER) not only resulted in the increased death of B16F10 and 4T1 tumor cells, but also induced higher levels of autophagy in vitro. Importantly, the local delivery of the CARE drugs significantly inhibited tumor growth in B16F10 and 4T1 tumor-bearing mice. Systemic antitumor T-cell immunity was observed in vivo, including neoantigen-specific T-cell responses. Furthermore, bioinformatic analysis of human breast cancer and melanoma tissues showed that autophagy-associated gene expression was upregulated in tumor samples. Increased autophagy and immune cell infiltration in tumor tissues were positively correlated with good prognosis of tumor patients. This work highlights a new approach to improve the effects of local chemotherapy and enhance systemic antitumor immunity.

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“…Initial studies utilized autologous tumor cell cDNA libraries for screening neoantigen-specific T cells. These approaches were cumbersome and impeded the progress of neoantigen discovery and application (82,83,89). Later, Rosenberg and colleagues devised a conceptually new strategy outlined in Figure 3 that did not require the laborious cDNA library screens (85).…”

Section: Til Act Targeting Tumor Neoantigensmentioning

confidence: 99%

“…Using these approaches, neoantigens and T cell reactivity to these neoantigens have been identified in a variety of cancers including NSCLC, ovarian cancer, squamous cell carcinoma of the head and neck, cholangiocarcinoma, and colorectal cancer (56,81,88,93,94). Recently, researchers have demonstrated that tandem minigen (TMG) libraries encoding putative neoantigens could be utilized to screen for therapeutic TILs and identification of neoantigen-specific T cells (87)(88)(89).…”

Section: Til Act Targeting Tumor Neoantigensmentioning

confidence: 99%

Cell Therapy With TILs: Training and Taming T Cells to Fight Cancer

2021

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The rationale behind cancer immunotherapy is based on the unequivocal demonstration that the immune system plays an important role in limiting cancer initiation and progression. Adoptive cell therapy (ACT) is a form of cancer immunotherapy that utilizes a patient’s own immune cells to find and eliminate tumor cells, however, donor immune cells can also be employed in some cases. Here, we focus on T lymphocyte (T cell)-based cancer immunotherapies that have gained significant attention after initial discoveries that graft-versus-tumor responses were mediated by T cells. Accumulating knowledge of T cell development and function coupled with advancements in genetics and data science has enabled the use of a patient’s own (autologous) T cells for ACT (TIL ACTs). In TIL ACT, tumor-infiltrating lymphocytes (TILs) are collected from resected tumor material, enhanced and expanded ex-vivo, and delivered back to the patient as therapeutic agents. ACT with TILs has been shown to cause objective tumor regression in several types of cancers including melanoma, cervical squamous cell carcinoma, and cholangiocarcinoma. In this review, we provide a brief history of TIL ACT and discuss the current state of TIL ACT clinical development in solid tumors. We also discuss the niche of TIL ACT in the current cancer therapy landscape and potential strategies for patient selection.

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The Ways of Isolating Neoantigen-Specific T Cells

Cited by 26 publications

References 86 publications

Prognostic and therapeutic TILs of cervical cancer—Current advances and future perspectives

Prognostic and therapeutic TILs of cervical cancer—Current advances and future perspectives

A Local and Low-Dose Chemotherapy/Autophagy-Enhancing Regimen Treatment Markedly Inhibited the Growth of Established Solid Tumors Through a Systemic Antitumor Immune Response

Cell Therapy With TILs: Training and Taming T Cells to Fight Cancer

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