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Engineering autologous tumor cell vaccine to locally mobilize antitumor immunity in tumor surgical bed.

ABSTRACT: Autologous tumor cell-based vaccines (ATVs) are emerging as a transformable approach for personalized immunotherapy, but their therapeutic efficacy remains unsatisfying in patients with cancer. Here, we design a photodynamic therapy (PDT)-motivated ATV (P-ATV) in Fmoc-KCRGDK-phenylboronic acid (FK-PBA) hydrogel, which mobilizes local immune activation to inhibit relapse of postoperative tumors. The FK-PBA targeting overexpressed sialic acid on tumor cells can enable on-demand gelation in residue tumor areas and maintain continuous vaccination in surgical bed. Unlike neoantigen-based vaccine or adoptive cell therapy that takes several months to prepare, P-ATV can be easily manufactured within a few days and efficiently boost neoepitope-specific CD8⁺ T cells to activate personalized immunotherapy. This simple and powerful approach of engineered ATVs provides an alternative strategy for personalized immunotherapy and is readily transformable to various kinds of cell-based antigens to inhibit the relapse of postoperative tumors.

SUBMITTER: Fang L

PROVIDER: S-EPMC7304971 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Engineering irradiated tumor-derivedmicroparticles as personalized vaccines toenhance antitumor immunity

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2023-10-27 | GSE239631 | GEO

Engineering irradiated tumor-derived microparticles as personalized vaccines to enhance antitumor immunity

2023-10-27 | GSE240108 | GEO

Bifunctional cancer cell-based vaccine concomitantly drives direct tumor killing and antitumor immunity.

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| S-EPMC10068810 | biostudies-literature

<i>In Situ</i> Tumor Vaccine Expressing Anti-CD47 Antibody Enhances Antitumor Immunity.

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| S-EPMC9273963 | biostudies-literature

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Uric acid enhances the antitumor immunity of dendritic cell-based vaccine.

Project description:Uric acid (UA) released from dying cells has been recognized by the immune system as a danger signal. In response to UA, dendritic cells (DC) in the immune system mature and enhance the T cell response to foreign antigens. It is conceivable that the antitumor immunity of a tumor vaccine could be promoted by the administration of UA. To test this concept, we applied UA as an adjuvant to a DC-based vaccine, and discovered that the administration of UA as an adjuvant significantly enhanced the ability of the tumor lysate-pulsed DC vaccine in delaying the tumor growth. The antitumor activity was achieved with adoptively transferred lymphocytes, and both CD8(+) T cells and NK cells were required to achieve effective immunity. This resulted in an increased accumulation of activated CD8(+) T cells and an elevated production of IFN-γ. Collectively, our study shows that the administration of UA enhances the antitumor activity of tumor lysate-pulsed DC vaccine, thus providing the preclinical rationale for the application of UA in DC-based vaccine strategies.

| S-EPMC4639747 | biostudies-other

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Project description:Wilms' tumor protein (WT1) is overexpressed in most leukemias and many solid tumors and is a promising target for tumor immunotherapy. WT1 peptide-based cancer vaccines have been reported but have limited application due to HLA restriction of the peptides. We sought to vaccinate using adenoviral (Ad) vectors encoding tumor-associated antigens such as WT1 that can stimulate tumor-associated antigen-specific immunity across a broad array of HLA types and multiple class I and class II epitopes.We developed a novel Ad vector encoding a truncated version of WT1 (Ad-tWT1) lacking the highly conserved COOH terminus zinc finger domains and tested its ability to stimulate WT1-specific immune responses and antitumor immunity in two murine models of WT1-expressing tumors.Despite encoding a transcription factor, we found that Ad-tWT1-transduced murine and human dendritic cells showed cytoplasmic expression of the truncated WT1 protein. In addition, vaccination of C57BL/6 mice with Ad-tWT1 generated WT1-specific cell-mediated and humoral immune responses and conferred protection against challenge with the leukemia cell line, mWT1-C1498. Moreover, in a tumor therapy model, Ad-tWT1 vaccination of TRAMP-C2 tumor-bearing mice significantly suppressed tumor growth.This is the first report of a WT1-encoding Ad vector that is capable of inducing effective immunity against WT1-expressing malignancies. Based on these findings, Ad-tWT1 warrants investigation in human clinical trials to evaluate its applications as a vaccine for patients with WT1-expressing cancers.

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Engineering irradiated tumor-derivedmicroparticles as personalized vaccines toenhance antitumor immunity

Project description:Engineering irradiated tumor-derivedmicroparticles as personalized vaccines toenhance antitumor immunity

| PRJNA1000457 | ENA

A dendritic cell vaccine pulsed with autologous hypochlorous acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside.

Project description:Whole tumor lysates are promising antigen sources for dendritic cell (DC) therapy as they contain many relevant immunogenic epitopes to help prevent tumor escape. Two common methods of tumor lysate preparations are freeze-thaw processing and UVB irradiation to induce necrosis and apoptosis, respectively. Hypochlorous acid (HOCl) oxidation is a new method for inducing primary necrosis and enhancing the immunogenicity of tumor cells.We compared the ability of DCs to engulf three different tumor lysate preparations, produce T-helper 1 (TH1)-priming cytokines and chemokines, stimulate mixed leukocyte reactions (MLR), and finally elicit T-cell responses capable of controlling tumor growth in vivo.We showed that DCs engulfed HOCl-oxidized lysate most efficiently stimulated robust MLRs, and elicited strong tumor-specific IFN-? secretions in autologous T cells. These DCs produced the highest levels of TH1-priming cytokines and chemokines, including interleukin (IL)-12. Mice vaccinated with HOCl-oxidized ID8-ova lysate-pulsed DCs developed T-cell responses that effectively controlled tumor growth. Safety, immunogenicity of autologous DCs pulsed with HOCl-oxidized autologous tumor lysate (OCDC vaccine), clinical efficacy, and progression-free survival (PFS) were evaluated in a pilot study of five subjects with recurrent ovarian cancer. OCDC vaccination produced few grade 1 toxicities and elicited potent T-cell responses against known ovarian tumor antigens. Circulating regulatory T cells and serum IL-10 were also reduced. Two subjects experienced durable PFS of 24 months or more after OCDC.This is the first study showing the potential efficacy of a DC vaccine pulsed with HOCl-oxidized tumor lysate, a novel approach in preparing DC vaccine that is potentially applicable to many cancers.

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| S-EPMC7478738 | biostudies-literature

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