Engineering an active immunotherapy for personalized cancer treatment and prevention of recurrence

Abstract

Breast cancer has been shown to be resistant to immunotherapies. To overcome this challenge, we developed an active immunotherapy for personalized treatment based on a smart nanovesicle. This is achieved by anchoring membrane-bound bioactive interleukin 2 (IL2) and enriching T cell–promoting costimulatory factors on the surface of the dendritic cell–derived small extracellular vesicles. This nanovesicle also displays major histocompatibility complex–bound antigens inherited from tumor lysate–pulsed dendritic cell. When administrated, the surface-bound IL2 is able to guide the nanovesicle to lymphoid organs and activate the IL2 receptor on lymphocytes. Furthermore, it is able to perform antigen presentation in the replacement of professional antigen-presenting cells. This nanovesicle, named IL2-ep13nsEV, induced a strong immune reaction to rescue 50% of the mice in our humanized patient-derived xenografts, sensitized cancer cells to immune checkpoint inhibitor treatment, and prevented the recurrence of resected tumors. This paradigm presents a feasible strategy for the treatment and prevention of metastatic breast cancer.

Engineering exosomes to reshape the immune microenvironment in breast cancer: Molecular insights and therapeutic opportunities

“…The findings indicated that the combination of engineered exosomes and ICIs rendered tumour cells more responsive to the effects of ICIs. Mechanistically, this combination led to an augmentation in the number of tumour‐infiltrating lymphocytes and activated T cells in the spleen 85 . This provides a viable strategy for the treatment and prevention of metastatic BC.…”

“…This work demonstrates the preclinical feasibility of utilizing endogenous exosomes for targeted BC immunotherapy. In addition, surface modification of IL‐2 on DC‐derived exosomes enables targeted delivery of engineered exosomes to lymphocytes and enhances binding to IL‐2 receptors on CD8+T cells, thereby inducing CD8+T cell activation 85 …”

“…In addition, surface modification of IL‐2 on DC‐derived exosomes enables targeted delivery of engineered exosomes to lymphocytes and enhances binding to IL‐2 receptors on CD8+T cells, thereby inducing CD8+T cell activation. 85 …”

Stimuli-Responsive Polymeric Nanomedicine for Enhanced Cancer Immunotherapy

“…Subsequently, cancer cell death resumes during the priming phase of the cancer immunity cycle. However, because the cancer immunity cycle is impaired in cancer patients, the main focus of cancer immunotherapy is to induce cancer cell death as the first step and restore the cancer immunity cycle. , An appropriate cancer immunity cycle induces effective cancer cell death and strengthens the patient’s immune memory, showing excellent recurrence prevention. , …”

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.…”