N-dihydrogalactochitosan as a potent immune activator for dendritic cells.

Immunotherapy has become one of the fastest growing areas of cancer research. A promising in situ autologous cancer vaccine (inCVAX) uses a novel immune activator, N-dihydrogalactochitosan (GC), that possesses the ability to stimulate dendritic cells (DC). inCVAX is a combination treatment procedure involving treatment of the tumor with a thermal near-infrared laser to liberate whole cell tumor antigens, followed by injection of GC (a glucosamine polymer with galactose attached to the amino groups) into the treated tumor thereby inducing a systemic antitumor immune response. Regression of both the treated tumor and distant untreated metastases has been observed in both nonclinical and clinical settings following inCVAX. We studied the stimulatory action of GC on relatively immature DCs (DC2.4 cell line) in vitro. GC at 1 mg/mL was a potent stimulator for DC with limited toxicity, giving increased expression of major histocompatibility complex class 2, CD80, and CD11c. Confocal imaging also revealed qualitatively increased uptake of antigen (Texas red-labeled ovalbumin) by DCs after the introduction of GC. To visualize cellular uptake, GC was conjugated with FITC-fluorophore revealing its cellular internalization after 8 hours. In some cases GC was more effective than the toxic TLR4 agonist, lipopolysaccharide. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 963-972, 2017.

Advances in strategies and methodologies in cancer immunotherapy.

Since the invention of Coley's toxin by William Coley in early 1900s, the path for cancer immunotherapy has been a convoluted one. Although still not considered standard of care, with the FDA approval of trastuzumab, Provenge and ipilimumab, the medical and scientific community has started to embrace the possibility that immunotherapy could be a new hope for cancer patients with otherwise untreatable metastatic diseases. This review aims to summarize the development of some major strategies in cancer immunotherapy, from the earliest peptide vaccine and transfer of tumor specific antibodies/T cells to the more recent dendritic cell (DC) vaccines, whole cell tumor vaccines, and checkpoint blockade therapy. Discussion of some major milestones and obstacles in the shaping of the field and the future perspectives is included. Photoimmunotherapy is also reviewed as an example of emerging new therapies combining phototherapy and immunotherapy.

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

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 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 is 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).

Selectivity via cooperative interactions: detection of dicarboxylates in water by a pinwheel chemosensor.

The recognition properties of a cooperative pinwheel chemosensor for dicarboxylates are described. The sensor possesses four guanidinium recognition elements to cooperatively bind two dicarboxylates of varying size. The effect of cooperativity and the read-out mechanism contributes to favorable binding constants for dicarboxylates in water, as well as a high degree of selectivity over monocarboxylates. Appropriate methods of reporting affinity for cooperative systems are discussed.