A short course of neoadjuvant IRX-2 induces changes in peripheral blood lymphocyte subsets of patients with head and neck squamous cell carcinoma.

Objective: IRX-2, a primary cell-derived biologic with pleotropic immune activity, was shown to induce increased lymphocyte infiltrations into the tumor of patients with head and neck squamous cell cancer (HNSCC) after 10 days of neoadjuvant therapy (Berinstein et al. 2011). In the same patients enrolled in the Phase II study, peripheral blood lymphocyte subsets were monitored pre- and post-IRX-2 therapy to evaluate changes induced by IRX-2.

Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen.

Twenty-seven subjects with squamous cell cancer of the head and neck received the neoadjuvant IRX-2 immunotherapy regimen prior to surgery in a Phase 2 trial. Pretreatment tumor biopsies were compared with the primary tumor surgical specimens for lymphocyte infiltration, necrosis and fibrosis, using hematoxylin and eosin stain and immunohistochemistry in 25 subjects. Sections were examined by three pathologists.

Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer.

Background: Cellular immune suppression is observed in head and neck squamous cell cancer (HNSCC) and contributes to poor prognosis. Restoration of immune homeostasis may require primary cell-derived cytokines at physiologic doses. An immunotherapy regimen containing a biologic, with multiple-active cytokine components, and administered with cytoxan, zinc, and indomethacin was developed to modulate cellular immunity.

Mechanisms of T-cell protection from death by IRX-2: a new immunotherapeutic.

Objectives: IRX-2 is a novel immunotherapeutic containing physiologic quantities of several cytokines which protects human T lymphocytes from tumor-induced or drug-induced apoptosis. Here, we investigate the mechanisms responsible for IRX-2-mediated protection of T lymphocytes exposed to tumor-derived microvesicles (TMV).

Methods: Jurkat cells or primary human T cells ± IRX-2 were co-incubated with TMV and then examined by flow cytometry or Western blots for expression of molecules regulating cell survival (FLIP, Bcl-2, Bcl-xL, Mcl-1) or death (Fas, caspase 8, caspase 9, Bax, Bid).

IRX-2 increases the T cell-specific immune response to protein/peptide vaccines.

Therapeutic cancer vaccines are attractive due to the prospect of specificity and their lack of toxicity; however, their clinical development has been hampered by several biologic and clinical challenges. One of the most important biologic challenges is the relative lack of effective cellular immune adjuvants. Effective physiologic immune responses are characterized by the local generation of a complex cytokine environment that activates and regulates multiple immune cell types.

A phase 1 safety study of an IRX-2 regimen in patients with squamous cell carcinoma of the head and neck.

Objectives: Head and neck squamous cell carcinoma (HNSCC) is associated with profound defects in cellular immunity. IRX-2, a primary cell-derived biologic containing multiple cytokines, has enhanced immune responses and induced tumor rejection in preclinical studies. This phase 1 open label study aimed to determine the clinical and laboratory safety of an IRX-2 regimen in patients with HNSCC.

Preclinical studies with IRX-2 and thymosin alpha1 in combination therapy.

Thymosin alpha1 (Talpha1) is a 28 amino acid biologically active protein with pleiotropic immune enhancing activity. IRX-2 is a primary cell-derived biologic containing multiple cytokines that enhance dendritic cell maturation, promote T-cell growth and differentiation, and inhibit tumor-mediated apoptosis of T cells. IRX-2 is being developed as an immunotherapeutic agent as a novel T-cell adjuvant platform for vaccines as well.

IRX-2, a novel in vivo immunotherapeutic, induces maturation and activation of human dendritic cells in vitro.

IRX-2 is a uniform, well-defined set of natural cytokines currently in Phase II clinical trials for squamous cell carcinoma of the head and neck (HNSCC). In preliminary clinical studies of HNSCC patients, IRX-2 therapy has shown promising results, increasing overall survival of patients from 32% to 61% at 48 months. Although it is known that specific cytokines in IRX-2 enhance T cell activity [e.

Immunopharmacology of thymosin alpha1 and cytokine synergy.

Thymosin alpha1 (Talpha1) is a 28 amino acid biologically active protein cleaved from positions 2-29 of a precursor protein, prothymosin alpha. Since its discovery, Talpha1 has been administered to animals and humans in a wide variety of settings and its pharmacologic effects are to enhance cellular immunity. Talpha1 administration is highly effective in settings where irradiation, chemotherapy, tumor burden, or immune senescence have caused a reduction of T cell number and/or function.

T cell targeted immune enhancement yields effective T cell adjuvants.

Given the critical role of cell-mediated immunity (CMI) in defense against attack from pathogens that establish chronic infections, it has become abundantly clear that current vaccine methodology will not be sufficient to develop the appropriate immune response for protection and/or clearance of infection. By extension, this logic also applies to cancer vaccines where T cell immune-mediated destruction is a critical mechanism for control of the disease. This review describes our current thoughts on the events associated with immune activation and evaluates the various approaches to achieve successful immune activation with defined or targeted antigens as opposed to using inactivated or attenuated organisms.

T cell immunostimulation by methyl inosine 5'-monophosphate: application to infectious diseases.

Methyl inosine 5'-monophosphate (MIMP) was designed and synthesized in an endeavor to generate compounds with immunostimulatory activity based on the precedent of purines, particularly inosine playing a central role in the development and function of the immune system. This review will summarize the immune-enhancing effects of MIMP on a variety of immunological responses both in vitro and in vivo. Among these studies, MIMP displays protective effects in several in vivo models of infectious disease following administration by one of several routes including oral.

Lymph node histology in head and neck cancer: impact of immunotherapy with IRX-2.

Objective: To determine if lymph nodes (LN) of patients receiving IRX-2 immunotherapy reflect changes in histology.

Setting: National Cancer Institute, Mexico City, Mexico.

Patients: Thirty patients with advanced squamous cell carcinoma of the head and neck (H and N SCC) and 10 non-cancer controls.

Immunodeficiency and cancer: prospects for correction.

Cellular immunodeficiency is associated with human cancer. Extensive reviews on cancer of the head and neck, lung, esophagus and breast convince the author that for these diseases the immunodeficiency is reasonably well established yet the mechanisms are poorly understood. Evidence indicates that other tumors are similarly associated with cellular immune deficiency.

Protection by methyl inosine monophosphate (MIMP) against aerosol influenza virus infection in mice.

Methyl inosine monophosphate (MIMP) is a novel thymomimetic purine immunomodulator capable of enhancing a wide variety of immune responses. Intravenous (i.v.