Immune Therapy for Ovarian Cancer: Promise and Pitfalls

Thibodeaux, Suzanne R.; Curiel, Tyler J.

doi:10.3109/08830185.2011.567361

Cited by 23 publications

(13 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, specifics of the interplay between tumor micro-environment and many aspects of the host immune response were poorly described at that time. More recent advances in the understanding of immune environment modulation (such as the ability to down-regulate immunosuppressive cells through the use of antibodies), the processes of immune effector cell expansion, and the availability of commercially manufactured cellular therapy products (such as umbilical cord blood units or dendritic cells) may improve the efficacy of cellular therapy [2,3].…”

Section: Introductionmentioning

confidence: 99%

Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer

et al. 2015

View full text Add to dashboard Cite

Studies have shown enhanced survival of ovarian cancer patients in which the tumors are infiltrated with tumor infiltrating lymphocytes and natural killer cells showing the importance of immune surveillance and recognition in ovarian cancer. Therefore, in this study, we tested cellular immunotherapy and varying combinations of cytokines (IL-2 and/or pegylated-IFNα-2b) in a xenograft mouse model of ovarian cancer. SKOV3-AF2 ovarian cancer cells were injected intra-peritoneally (IP) into athymic nude mice. On day 7 post-tumor cell injection, mice were injected IP with peripheral blood mononuclear cells (PBMC; 5 × 10(6) PBMC) and cytokine combinations [IL-2 ± pegylated-IFNα-2b (IFN)]. Cytokine injections were continued weekly for IFN (12,000 U/injection) and thrice weekly for IL-2 (4000 U/injection). Mice were euthanized when they became moribund due to tumor burden at which time tumor and ascitic fluid were measured and collected. Treatment efficacy was measured by improved survival at 8 weeks and overall survival by Kaplan-Meier analysis. We observed that the mice tolerated all treatment combinations without significant weight loss or other apparent illness. Mice receiving PBMC plus IL-2 showed improved median survival (7.3 weeks) compared to mice with no treatment (4.2 weeks), IL-2 (3.5 weeks), PBMC (4.0 weeks), or PBMC plus IL-2 and IFN (4.3 weeks), although PBMC plus IL-2 was not statistically different than PBMC plus IFN (5.5 weeks, p > 0.05). We demonstrate that cytokine-stimulated cellular immune therapy with PBMC and IL-2 was well tolerated and resulted in survival advantage compared to untreated controls and other cytokine combinations in the nude-mouse model.

show abstract

Section: Introductionmentioning

confidence: 99%

Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Restoring immune function in cancer microenvironment has immense potential for a new cancer therapy (14). We have attempted to elucidate the mechanism of immune escape in ovarian cancer and reported that in the ovarian cancer microenvironment, molecules such as ULBP2 (NKG2D ligand), COX-1, COX-2, and programmed cell death 1 ligand 1 (PD-L1) or the combined expression of these molecules are related to limited infiltration by lymphocytes and an unfavorable prognosis (15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

PD-L1 on Tumor Cells Is Induced in Ascites and Promotes Peritoneal Dissemination of Ovarian Cancer through CTL Dysfunction

Abiko

Mandai

Hamanishi

et al. 2013

Clinical Cancer Research

200

178

View full text Add to dashboard Cite

Purpose: Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be expressed in cancer cells. The purpose of this study is to elucidate the function of PD-L1 in peritoneal dissemination.Experimental Design: Ovarian cancer cases were studied by microarray and immunohistochemistry. PD-L1 expression in mouse ovarian cancer cell line in various conditions was assessed by flow cytometry. PD-L1-overexpression cell line and PD-L1-depleted cell line were generated, and cytolysis by CTLs was analyzed, and alterations in CTLs were studied by means of timelapse and microarray. These cell lines were injected intraperitoneally to syngeneic immunocompetent mice.Results: Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and peritoneal positive cytology. PD-L1 expression in mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and coculture with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression inhibited gathering and degranulation of CTLs. Gene expression profile of CTLs caused by PD-L1-overexpressing ovarian cancer was associated with CTLs exhaustion. In mouse models, PD-L1 depletion resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival.Conclusion: PD-L1 expression in tumor cell promotes peritoneal dissemination by repressing CTL function. PD-L1-targeted therapy is a promising strategy for preventing and treating peritoneal dissemination.

show abstract

“…Besides, many molecular changes create an immunosuppressive milieu that inhibits anti-tumor immunity. Some of the strongest evidence linking anti-tumor immunity and cancer have been made in ovarian cancer [41][42][43][44]. For ovarian cancer, chemotherapy remains the treatment modality of choice.…”

Section: New Agents Against Ovarian Cancermentioning

confidence: 99%

Editorial: Advances in Epithelial Ovarian Cancer Therapy

Kroep¹

2012

curr pharm des

View full text Add to dashboard Cite

Advanced epithelial ovarian carcinoma has a dismal prognosis. Notwithstanding the good initial response to primary therapy, 75% of the patients with advanced disease will develop recurrent disease, causing approximately 60-80% of patients to die within 5 years of initial diagnosis. The chemotherapy regimens of the past century are summarized and the focus is on current systemic therapies and future developments in advanced epithelial ovarian cancer. Recently various promising treatments emerged. Attempts to optimize chemotherapy have included weekly scheduling of paclitaxel and intraperitoneal chemotherapy. Trials using angiogenesis inhibition and poly-ADP ribose polymerase (PARP) inhibitors show an advantage in progression-free survival while further overall survival data are awaited. Trabectedin, Hyperthermic intraperitoneal chemotherapy (HIPEC) and chemo-immunotherapy may be become a promising therapy for the treatment of ovarian cancer. This Editorial encapsulates these new developments in ovarian cancer that are described extensively in the current theme issue Advances in Epithelial Ovarian Cancer Therapy.

show abstract

Immune Therapy for Ovarian Cancer: Promise and Pitfalls

Cited by 23 publications

References 111 publications

Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer

Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer

PD-L1 on Tumor Cells Is Induced in Ascites and Promotes Peritoneal Dissemination of Ovarian Cancer through CTL Dysfunction

Editorial: Advances in Epithelial Ovarian Cancer Therapy

Contact Info

Product

Resources

About