tumor ablation techniques, like radiotherapy, cryo- and heat-based thermal ablation are successfully applied in oncology for local destruction of tumor masses. Although diverse in technology and ...mechanism of inducing cell death, ablative techniques share one key feature: they generate tumor debris which remains
. This tumor debris functions as an unbiased source of tumor antigens available to the immune system and has led to the concept of
cancer vaccination. Most studies, however, report generally modest tumor-directed immune responses following local tumor ablation as stand-alone treatment. Tumors have evolved mechanisms to create an immunosuppressive tumor microenvironment (TME), parts of which may admix with the antigen depot. Provision of immune stimuli, as well as approaches that counteract the immunosuppressive TME, have shown to be key to boost ablation-induced anti-tumor immunity. Recent advances in protein engineering have yielded novel multifunctional antibody formats. These multifunctional antibodies can provide a combination of distinct effector functions or allow for delivery of immunomodulators specifically to the relevant locations, thereby mitigating potential toxic side effects. This review provides an update on immune activation strategies that have been tested to act in concert with tumor debris to achieve
cancer vaccination. We further provide a rationale for multifunctional antibody formats to be applied together with
ablation to boost anti-tumor immunity for local and systemic tumor control.
Cancer vaccines are emerging as an attractive modality for tumor immunotherapy. However, their practical application is seriously impeded by the complex fabrication and unsatisfactory outcomes. ...Herein, we construct bacterial outer membrane vesicles (OMVs)-based in situ cancer vaccine with phytochemical features for photodynamic effects-promoted immunotherapy. By simply fusing thylakoid membranes with OMVs, bacteria-plant hybrid vesicles (BPNs) are prepared. After systemic administration, BPNs can target tumor tissues and stimulate the activation of immune cells, including dendritic cells (DCs). The photodynamic effects derived from thylakoid lead to the disruption of local tumors and then the release of tumor-associated antigens that are effectively presented by DCs, inducing remarkable tumor-specific CD8+T cell responses. Moreover, BPNs can efficiently ameliorate the immunosuppressive tumor microenvironment and further boost immune responses. Therefore, both tumor development and metastasis can be efficiently prevented. This work provides a novel idea for developing a versatile membrane-based hybrid system for highly efficient tumor treatment.
Post‐surgical tumor recurrence remains a major clinical concern for patients with malignant solid tumors. Herein, an immunotherapeutic hydrogel (SAPBA/ZMC/ICG) is developed by incorporating metal ...ion‐cyclic dinucleotide (CDN) nanoparticles (Zn‐Mn‐CDN, ZMC) and a photosensitizer (indocyanine green, ICG) into phenylboronic acid (PBA)‐conjugated sodium alginate (SAPBA) for photothermal therapy (PTT)‐triggered in situ vaccination to inhibit post‐surgical recurrence and metastasis of malignant tumors. The gelation of SAPBA/ZMC/ICG in the residual tumors can achieve accurate local PTT and the local sustained release of CDN and Mn2+ with minimal detrimental off‐target toxic effects. Furthermore, CDN, which is an agonist of the stimulator of interferon genes (STING), along with Mn2+ can activate the STING pathway and trigger type‐I‐IFN‐driven immune responses against tumors. Therefore, the immunotherapeutic hydrogel with enhanced immune response by STING agonist and PTT‐induced immunogenic cell death (ICD) reprograms the post‐surgical immunosuppressive microenvironment, substantially decreasing the post‐surgical recurrence and metastasis of solid tumors in multiple murine tumor models when administered during surgical resection. Taken together, PTT‐triggered and STING‐mediated in situ cancer vaccination is an effective therapeutic intervention for post‐surgical recurrence and metastasis of tumors.
Immunotherapeutic hydrogel (denoted as SAPBA/ZMC/ICG) with photothermally induced immunogenic cell death and stimulator of interferon genes (STING) activation is developed for post‐surgical treatment. The SAPBA/ZMC/ICG gelled in situ at residual tumor site achieves accurate local photothermal therapy (PTT) and sustains release of STING agonist cyclic dinucleotides (CDNs) and Mn2+. The CDNs and Mn2+ reprogram the post‐surgical immunosuppressive milieu, and in combination with PTT‐induced immunogenic cell death, resulting in a systemic anti‐tumor immune response and thereby preventing post‐surgical recurrence and metastasis of tumors.
In situ anti‐tumor vaccination is an attractive type of cancer immunotherapy which relies on the effectiveness of dendritic cells (DCs) to engulf tumor antigens, become activated, and present ...antigens to T cells in lymphoid tissue. Here, a multifunctional nanocomplex based on calcium crosslinked polyaspartic acid conjugated to either a toll‐like receptor (TLR)7/8 agonist or a photosensitizer is reported. Intratumoral administration of the nanocomplex followed by laser irradiation induces cell killing and hence generation of a pool of tumor‐associated antigens, with concomitant promotion of DCs maturation and expansion of T cells in tumor‐draining lymph nodes. Suppression of tumor growth is observed both at the primary site and at the distal site, thereby hinting at successful induction of an adaptive anti‐tumor response. This strategy holds promise for therapeutic application in a pre‐operative and post‐operative setting to leverage to mutanome of the patient's own tumor to mount immunological memory to clear residual tumor cells and metastasis.
A novel in situ tumor vaccine that co‐deliver TLR7/8 agonist and photosensitizer is fabricated, which can target tumor cells and the immune system separately. The NanopIR/mpIM can harness the tumor as the source of antigens, and enhance the immune system by activating antigen‐presenting cells. This approach is a promising strategy for cancer immunotherapy of primary and distal tumors.
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