Original Articles

Immunotherapy for gynecologic cancers

In choosing the Breakthrough of the Year in 2013, the editors of Science recognized years of efforts toward the tantalizing goal of enlisting the body’s own immune system to fight cancer [1]. Since then, we have seen the acceleration of multiple approaches from the laboratory to the clinic including immune checkpoint blockade, adoptive cellular therapy, and cancer vaccines. How these strategies fare in clinical trials may ultimately lead to paradigm shifts in therapy.

The Antitumor Efficacy of IL2/IL21-Cultured Polyfunctional Neu-Specific T Cells Is TNFa/IL17 Dependent

PURPOSE:

Infusion of HER2-specific T cells, derived from vaccine-primed patients and expanded with IL2/IL12, has induced tumor regression in a minority of patients with metastatic treatment-refractory HER2+ breast cancer. We questioned whether alteration of cytokine growth factors used to culture vaccine-primed T cells could improve antitumor activity.

Preservation of tumor-host immune interactions with luciferase-tagged imaging in a murine model of ovarian cancer.

BACKGROUND:

Ovarian cancer is immunogenic and residual tumor volume after surgery is known to be prognostic. Ovarian cancer often follows a recurring-remitting course and microscopic disease states may present ideal opportunities for immune therapies. We sought to establish the immune profile of a murine model of ovarian cancer that allows in vivo tumor imaging and the quantitation of microscopic disease.

Natural history of tumor growth and immune modulation in common spontaneous murine mammary tumor models.

Recent studies in patients with breast cancer suggest the immune microenvironment influences response to therapy. We aimed to evaluate the relationship between growth rates of tumors in common spontaneous mammary tumor models and immune biomarkers evaluated in the tumor and blood. TgMMTV-neu and C3(1)-Tag transgenic mice were followed longitudinally from birth, and MPA-DMBA-treated mice from the time of carcinogen administration, for the development of mammary tumors.

Therapeutic vaccines for ovarian cancer.

While therapeutic vaccines for ovarian cancer represent only a small fraction of active clinical trials, growing interest in this area and the accumulated data supporting the use of vaccines in cancer treatment portend further expansion of trials incorporating these strategies. This review explores the rationale for the use of vaccines for the treatment of ovarian cancer. It examines vaccine platforms that have been investigated and reviews the data from these studies. We also highlight recently reported phase 2 and 3 clinical trials with clinical outcomes as endpoints.

Protein-bound polysaccharide-K induces IL-1β via TLR2 and NLRP3 inflammasome activation.

Inflammasome activation has been shown to regulate both innate and adaptive immune responses. It is important to investigate whether immune-enhancing natural products can also activate inflammasome. The current study examined the potential of protein-bound polysaccharide-K (PSK), a hot water extract from Trametes versicolor, to activate inflammasome. Using THP-1 cells, we have demonstrated that PSK induces both pro-IL-1β and mature IL-1β in THP-1 cells in a caspase 1- and NLRP3-dependent manner. PSK also induces IL-1β and IL-18 in human PBMC.

Can immunity to breast cancer eliminate residual micrometastases?

An effective immune response has the potential for breast cancer sterilization with marked reduction in the potential for disease relapse. Adaptive type I immune cells uniquely have the capability of (i) cytotoxic T-cell activation and proliferation until all antigen expressing cells are eradicated, (ii) traversing endothelial barriers to penetrate tumor deposits wherever they occur, and (iii) immunologic memory, which allows the persistence of destructive immunity over the years it may take for breast cancer micrometastases to become clinically evident.

Proteomic profiling of the autoimmune response to breast cancer antigens uncovers a suppressive effect of hormone therapy

PURPOSE:  Proteomics technologies are well suited for harnessing the immune response to tumor antigens for diagnostic applications as in the case of breast cancer. We previously reported a substantial impact of hormone therapy (HT) on the proteome. Here, we investigated the effect of HT on the immune response toward breast tumor antigens.

HER-2/neu vaccine-primed autologous T-cell infusions for the treatment of advanced stage HER-2/neu expressing cancers

This phase I study evaluated the feasibility of expanding HER-2/neu (HER2) vaccine-primed peripheral blood T-cells ex vivo and assessed the safety of T-cell infusions. Eight patients with HER2(+) treatment refractory metastatic cancers were enrolled. T-cells could be expanded to predefined parameters in seven patients (88%).

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