InCVAX – A novel strategy for treatment of late-stage, metastatic cancers through photoimmunotherapy induced tumor-specific immunity

Abstract

A novel, promising potential cancer vaccine strategy was proposed to use a two-injection procedure for solid tumors to prompt the immune system to identify and systemically eliminate the primary and metastatic cancers. The two-injection procedure consists of local photothermal application on a selected tumor intended to liberate whole cell tumor antigens, followed by a local injection of an immunoadjuvant that consists of a semi-synthetic functionalized glucosamine polymer, N-dihydro-galacto-chitosan (GC), which is intended to activate antigen presenting cells and facilitate an increased uptake of tumor antigens. This strategy is thus proposed as an in situ autologous cancer vaccine (inCVAX) that may activate antigen presenting cells and expose them to tumor antigens in situ, with the intention of inducing a systemic tumor specific T-cell response. Here, the development of inCVAX for the treatment of metastatic cancers in the past decades are systematically reviewed. The antitumor immune responses of local photothermal treatment and immunological stimulation with GC are also discussed. This treatment approach is also commonly referred to as laser immunotherapy (LIT).

Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors

“…Because of this, many cancer treatments use "whole-cell" vaccines prepared from resected tissue that contains the entire antigen spectrum for each patient's primary tumor (35)(36)(37). By enabling the immune system to react with unique epitopes, these vaccines can evoke reactions against an array of antigens that do not need to be preidentified by the physician.…”

Treatment of advanced melanoma with laser immunotherapy and ipilimumab

“…Laser immunotherapy (LIT) is a novel and promising cancer treatment strategy that uses local photothermal application on selected tumor deposits as a source of tumor antigens, followed by a local application of an immunoadjuvant which works in tandem with tumor antigens liberated by local laser irradiation, creating an in situ autologous cancer vaccine . LIT with imiquimod, an FDA approved topical immunoadjuvant , has proven to be a promising treatment modality for advanced melanoma patients.…”

“…As previously established, LIT treatment for advanced melanoma patients typically results in a long‐term adoptive immune response against residual primary and metastatic tumor cells . Our experimental evidence suggests that LIT induces long‐term antitumor immunity, by enhancing antigen uptake and presentation that ultimately result in enhanced specific, antitumor T cell activation . LIT would likely improve the number and quality of anti‐tumor T cells, setting the stage for an enhanced response to a checkpoint inhibitors such as ipilimumab.…”

N‐dihydrogalactochitosan as a potent immune activator for dendritic cells

“…inCVAX is a promising therapeutic approach for the treatment of primary and metastatic cancer . The procedure involves the local application of photo‐thermal energy from a NIR laser to a visible tumor deposit, which is immediately followed by a local injection of GC into the tumor region as an immune activator.…”

“…InCVAX is a two‐step procedure involving delivery of low‐power thermal laser (for 10 minutes) to any accessible tumor to cause tumor cell death, release of antigens, and to increase the immunogenicity of tumor, followed immediately by injection of GC into the laser‐treated tumor region to stimulate antigen presenting cells. The two‐step procedure works synergistically to induce systemic antitumor T cell response that is capable of eliminating both primary and metastatic cancers in some patients with advanced, stage III/IV, breast cancer with minimal toxicity …”