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Amarillo, TX, United States

Dobrzanski M.J.,Texas Tech University | Dobrzanski M.J.,Bristol Hospital Cancer Care Center | Rewers-Felkins K.A.,Texas Tech University | Samad K.A.,Texas Tech University | And 6 more authors.
Cancer Immunology, Immunotherapy | Year: 2012

Adoptive T cell therapy for cancer patients optimally requires participation of CD4 T cells. In this phase I/II study, we assessed the therapeutic effects of adoptively transferred IL-10- and IFN-γ-producing CD4 effector cells in patients with recurrent ovarian cancer. Using MUC1 peptide and IL-2 for ex vivo CD4 effector cell generation, we show that three monthly treatment cycles of autologous T cell restimulation and local intraperitoneal re-infusion-modulated T cell-mediated immune responses that were associated with enhanced patient survival. One patient remains disease-free, another patient experienced prolonged survival for nearly 16 months with recurrent disease, and two patients expired within 3-5 months following final infusion. Prolonged survivors showed elevated levels of systemic CD3 +CD4 +CD25 + and CD3 +CD4 +CD25 - T cells when compared to that of pre-treatment levels and similarly treated short-term survivors. Such cell populations among these patients contained variable levels of "Inducible" Tr1 (CD4 +CD25 -FoxP3 -IL-10 +) and "Natural" (CD4 +CD25 +CD45RO +FoxP3 +) TReg cell numbers and ratios that were associated with prolonged and/or disease-free survival. Moreover, peptide-restimulated T cells from these patients showed an elevation in both IFN-γ production, memory cell phenotype, and select TNF family ligands associated with enhanced T cell survival and apoptosis-inducing activities. This suggests that intraperitoneally administered Th1-like cells, producing elevated levels of IL-10, may require and/or induce differential levels of distinct systemic TReg subpopulations that influence, in part, long-term tumor immunity and enhanced memory/effector CD4-mediated therapeutic potentials. Furthermore, treatment efficacy and enhanced memory cell phenotype did not appear to be dependent on TReg cell numbers but upon ratios of "Inducible" and "Natural" TReg subpopulations. © 2011 Springer-Verlag.

Wright S.E.,Womens Health Research Institute | Wright S.E.,Texas Tech University Health Sciences Center | Wright S.E.,Harrington Cancer Center | Rewers-Felkins K.A.,Womens Health Research Institute | And 3 more authors.
Oncology Letters | Year: 2016

Cytotoxic T-lymphocyte activation and extension of the cell life span is necessary in order to enable immunotherapy to perform effectively against cancer. In the present study, mucin 1 (MUC1)-stimulated human mononuclear cells (M1SHMCs) were costimulated with bead-attached monoclonal antibodies specific for cluster of differentiation (CD)3 and CD28 receptors. The study was undertaken to determine whether costimulation was capable of enhancing the killing of cancer cells in vitro and of protecting non-obese diabetic severe combined immunodeficient mice from tumor development. Lysis of MCF-7 tumor cells by M1SHMCs was reduced following costimulation with anti-CD3 and anti-CD28. Furthermore, costimulation with anti-CD3 and anti-CD28 eliminated the protective effects of M1SHMCs on MCF-7 breast cancer cell growth in the non-obese diabetic severe combined immunodeficient mice. The present study suggested that costimulation with anti-CD3 and anti-CD28 is not advisable following antigen activation of lymphocytes under the conditions used here. Using a lower anti-CD3/CD28 bead to T-cell ratio may prevent immune suppression, however, further studies are required to support this hypothesis. © Spandidos Publications 2015. All rights reserved.

Gupta P.,Texas Tech University Health Sciences Center | Wright S.E.,Texas Tech University Health Sciences Center | Wright S.E.,Harrington Cancer Center | Srivastava S.K.,Texas Tech University Health Sciences Center | Srivastava S.K.,Cancer Preventive Material Development Research Center
OncoImmunology | Year: 2015

Breast tumors are heterogeneous with a complex etiology. The immune system plays a crucial role in the development of tumors and can facilitate tumor growth pleiotropically. Myeloid derived suppressor cells (MDSCs) generate reactive oxygen species (ROS) and cytokines to suppress T cells, dendritic cells and natural killer (NK) cells. Hence, the inhibition of MDSCs could be an important strategy for anticancer therapeutics. Phenethyl isothiocyanate (PEITC), a bioactive compound present in cruciferous vegetables, is known to have anticancer properties. However, the effects of PEITC administration on the immune system have not been previously reported. In the current study, we evaluated the effects of administering PEITC to immunocompromised NOD-SCID IL2Rγ-/-(SCID/NSG) host mice bearing MDA-MB-231 xenografts on MDSCs in the peripheral blood. Our results reveal that oral administration of 12 μmol PEITC attenuated tumor growth by 76%. This was marked tumor-inhibitory phenotype was associated with asignificant reduction in the levels of MDSCs bearing the surface markers CD33, CD34 and CD11b in PEITC treated mice, indicating that overall tumor growth suppression by PEITC correlates with inhibition of MDSCs. To the best of our knowledge, this is the first study showing effects of PEITC on MDSCs. © 2015 Taylor & Francis Group, LLC.

Wright S.E.,Texas Tech University Health Sciences Center | Wright S.E.,Harrington Cancer Center | Rewers-Felkins K.A.,Texas Tech University Health Sciences Center | Chowdhury N.I.,Texas Tech University Health Sciences Center | And 2 more authors.
Oncology Letters | Year: 2012

CpG-ODNs activate various immune cell subsets and induce the production of numerous cytokines. To determine whether a CpG-ODN-activated innate immune system, without the adaptive immune system, was capable of protecting against cancer cell growth, NOD/SCID mice, which do not have T or B cell function but have a functional innate immune system, were used as a model system. NOD/SCID mice were injected subcutaneously with human prostate cancer cells followed by subcutaneous injection of incremental doses of CpG-ODNs. CpG-ODNs displayed a dose-related antitumoral effect leading to the prevention of tumor growth. These results indicate that ODNs are capable of activating the innate immune system and destroying human cancer cells in the absence of the adaptive immune system.

Ballard K.S.,East Carolina University | Tedjarati S.S.,Texas Tech University Health Sciences Center | Robinson W.R.,Texas Tech University Health Sciences Center | Robinson W.R.,Harrington Cancer Center | And 2 more authors.
International Journal of Gynecological Cancer | Year: 2010

The aim of this retrospective study was to evaluate differences in treatment of embryonal rhabdomyosarcoma (RMS) of the uterus in 2 premenopausal women. We discuss adjuvant chemotherapy and use of ChemoFx Assay (Precision Therapeutics, Pittsburgh, PA) to guide choice of active chemotherapeutic agents. Two premenopausal patients were identified with a pathologic diagnosis of embryonal RMS of the uterus. Both met inclusion criteria for the study. A 21-year-old woman underwent a staging abdominal hysterectomy for a variant of embryonal RMS. Vincristine, actinomycin D, and cyclophosphamide were given adjunctively for a complete response. A 20-year-old woman underwent a diagnostic dilation and curettage revealing embryonal RMS. Initial treatment included an abdominal hysterectomy and nodal sampling. Presentation to a subsequent gynecologic oncologist 7 months later revealed recurrence. Carboplatin, doxorubicin, and paclitaxel provided a partial response. After a second surgical resection, ChemoFx Assay identified ifosfamide and mitomycin C as active agents and resulted in a complete response. Recommended treatment includes surgery and chemotherapy with possible radiation therapy if deemed necessary. The benefit of adding neoadjuvant or adjuvant chemotherapy and radiation therapy allows for a conservative surgical approach and improved survival. Choosing active chemotherapy agents can be aided by ChemoFx Assay. The chemotherapy most commonly used for treatment of embryonal RMS is a combination of vincristine, actinomycin D, and cyclophosphamide.

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