Adoptive T cell transfer and host antigen-presenting cell recruitment with cryogel scaffolds promotes long-term protection against solid tumors

Abstract

Although adoptive T cell therapy provides the T cell pool needed for immediate tumor debulking, the infused T cells generally have a narrow repertoire for antigen recognition and limited ability for long-term protection. Here, we present a hydrogel that locally delivers adoptively transferred T cells to the tumor site while recruiting and activating host antigen-presenting cells with GMCSF or FLT3L and CpG, respectively. T cells alone loaded into these localized cell depots provided significantly better control of subcutaneous B16-F10 tumors than T cells delivered through direct peritumoral injection or intravenous infusion. T cell delivery combined with biomaterial-driven accumulation and activation of host immune cells prolonged the activation of the delivered T cells, minimized host T cell exhaustion, and enabled long-term tumor control. These findings highlight how this integrated approach provide both immediate tumor debulking and long-term protection against solid tumors, including against tumor antigen escape.

Cold Tumour Phenotype Explained Through Whole Genome Sequencing in Clinical Nasopharyngeal Cancer: A Preliminary Study

“…T cell therapy requires the presence of tumour antigen on the tumour cell surface. 31 This was abolished in our specimen, rendering this kind of therapy ineffective. Another example, radiotherapy with a hypofractionated dosing regimen generally of around 6-20 Gy per fraction, has been known to induce upregulation of MHC class I molecules to improve the tumour neoantigen presentation to CD8 T cells.…”

Biomimetic Tertiary Lymphoid Structures with Microporous Annealed Particle Scaffolds for Cancer Postoperative Therapy

“…Cancer is a serious threat to human health. , Surgical removal of the tumor is preferred, but it still faces the problem of high recurrence and metastasis rates due to the resident tumor cells or circulating tumor cells. − In addition to traditional chemotherapy and radiotherapy, immunotherapy plays an increasingly important role in cancer postoperative treatment. − Different from immune checkpoint inhibitors and cancer vaccines, immune cell-based immunotherapy, for instance, T cells, natural killer cells, and macrophages, can directly kill cancer cells and has been widely studied. , In order to increase the concentration of therapeutic immune cells at the tumor site and mitigate adverse effects caused by systemic administration, biomaterial scaffolds have been applied to achieve the target delivery and release of immune cells. − Although with much progress, the preparation of these therapeutic immune cells could only achieve a limited amount, which hinders their widespread use. In addition, a single therapeutic ingredient in these systems also makes them less effective.…”

Biomaterial-Based Sustained-Release Drug Formulations for Localized Cancer Immunotherapy

“…Antibody-based immune checkpoint inhibitors (ICI) have shown remarkable clinical responses against various tumor indications. Representative classes of ICI in the clinic include ipilimumab (Yervoy), pembrolizumab (Keytruda), and nivolumab (Opdivo) that block cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-1 (PD-1) pathways. − Adoptive T cell therapy involves in vivo isolation, ex vivo expansion and manipulation, and reinfusion of T cells back to patients to increase the quality and quantity of antitumor T cells in circulation. − It can source endogenous tumor-infiltrating T cells with cognate T cell receptors or genetically engineered T cells expressing chimeric antigen receptor (CAR). In particular, CAR-T cells such as tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta) have demonstrated robust antitumor efficacy and have been applied for the treatment of hematological tumors such as B cell leukemia and lymphoma in the clinic. − Oncolytic virus (OV) therapy utilizes viral strains that are genetically engineered to target tumors, replicate inside cancer cells, and induce cancer cell lysis.…”

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