Advances in strategies and methodologies in cancer immunotherapy.

Lam SS, Zhou F, Hode T, Nordquist RE, Alleruzzo L, Raker J, Chen WR

Abstract
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.

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

Zhou F, Li X, Naylor MF, Hode T, Nordquist RE, Alleruzzo L, Raker J, Lam SS, Du N, Shi L, Wang X, Chen WR.

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 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).


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Preliminary safety and efficacy results of laser immunotherapy for the treatment of metastatic breast cancer patients

Li X, Ferrel GL, Guerra MC, Hode T, Lunn JA, Adalsteinsson O, Nordquist RE, Liu H, Chen WR

Abstract
We report our preliminary results of a pilot clinical trial of late-stage breast cancer patients treated by laser immunotherapy (LIT), a local intervention using an 805 nm laser for non-invasive irradiation, indocyanine green for selective thermal effect, and immunoadjuvant (glycated chitosan) for immunological stimulation. Ten breast cancer patients were enrolled in this study; all patients were considered to be out of other available treatment options. Toxicity was individually evaluated through physical exams and laboratory tests. Adverse reactions only occurred in the area of treatment due to photothermal injury and local administration of immunoadjuvant. No grade 3 or 4 side effects were observed. Treatment efficacy of LIT was also evaluated by physical examination and tomography. In 8 patients available for evaluation, the objective response rate was 62.5% and the clinical beneficial response rate was 75%. While the study is still ongoing, the initial outcomes of this clinical trial show that LIT is well tolerated and is promising in the treatment of metastatic breast cancer.

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