Safety and immunologic correlates of Melanoma GVAX, a GM-CSF secreting allogeneic melanoma cell vaccine administered in the adjuvant setting

Lipson, Evan J.; Sharfman, William H.; Chen, Shuming; McMiller, Tracee L.; Pritchard, Theresa S.; Salas, January T.; Sartorius-Mergenthaler, Susan; Freed, Irwin; Ravi, Sowmya; Wang, Hao; Luber, Brandon; Sproul, Janice Davis; Taube, Janis M.; Pardoll, Drew M.; Topalian, Suzanne L.

doi:10.1186/s12967-015-0572-3

Cited by 82 publications

(58 citation statements)

References 60 publications

(60 reference statements)

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“…(37) In some clinical studies, however, GVAX immunotherapy has lead to a reduction in circulating MDSCs. (38) The relationship between GM-CSF expression and immunoregulatory mechanisms requires further study.…”

Section: Discussionmentioning

confidence: 99%

Vaccination with Irradiated Autologous Tumor Cells Mixed with Irradiated GM-K562 Cells Stimulates Antitumor Immunity and T Lymphocyte Activation in Patients with Recurrent Malignant Glioma

Curry

Gorrepati

Piesche

et al. 2016

Clinical Cancer Research

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Purpose: Recurrent malignant glioma carries a dismal prognosis, and novel therapies are needed. We examined the feasibility and safety of vaccination with irradiated autologous glioma cells mixed with irradiated GM-K562 cells in patients undergoing craniotomy for recurrent malignant glioma. Experimental Design: We initiated a phase I study examining the safety of 2 doses of GM-K562 cells mixed with autologous cells. Primary endpoints were feasibility and safety. Feasibility was defined as the ability for 60% of enrolled subjects to initiate vaccination. Dose-limiting toxicity was assessed via a 3+3 dose-escalation format, examining irradiated tumor cells mixed with 5 × 106 GM-K562 cells or 1 × 107 GM-K562 cells. Eligibility required a priori indication for resection of a recurrent high-grade glioma. We measured biological activity by measuring delayed type hypersensitivity (DTH) responses, humoral immunity against tumor-associated antigens, and T-lymphocyte activation. Results: Eleven patients were enrolled. Sufficient numbers of autologous tumor cells were harvested in 10 patients, all of whom went on to receive vaccine. There were no dose-limiting toxicities. Vaccination strengthened DTH responses to irradiated autologous tumor cells in most patients, and vigorous humoral responses to tumor-associated angiogenic cytokines were seen as well. T-lymphocyte activation was seen with significantly increased expression of CTLA-4, PD-1, 4-1BB, and OX40 by CD4+ cells and PD-1 and 4-1BB by CD8+ cells. Activation was coupled with vaccine-associated increase in the frequency of regulatory CD4+ T lymphocytes. Conclusions: Vaccination with irradiated autologous tumor cells mixed with GM-K562 cells is feasible, well tolerated, and active in patients with recurrent malignant glioma. Clin Cancer Res; 22(12); 2885–96. ©2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Vaccination with Irradiated Autologous Tumor Cells Mixed with Irradiated GM-K562 Cells Stimulates Antitumor Immunity and T Lymphocyte Activation in Patients with Recurrent Malignant Glioma

Curry

Gorrepati

Piesche

et al. 2016

Clinical Cancer Research

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“…Drugs used for cancer immunotherapy vary both in structure and by mechanism of action. For example, Iipilimumab (anti-CTLA4) directly interacts with and activates immune cells by removing co-inhibitory signal, while GVAX (GM-CSF tumor vaccine) improves tumor recognition by making the tumor more immunostimulatory (Ali and Lee, 2015; Lipson et al, 2015). A recent study by Fiering et al demonstrated the use of iron oxide nanoparticles and an alternating magnetic field to induce local hyperthermia in melanoma.…”

Section: Achievementsmentioning

confidence: 99%

Current understanding of interactions between nanoparticles and the immune system

Dobrovolskaia

Shurin

Shvedova

2016

Toxicology and Applied Pharmacology

252

189

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The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other endpoints, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure–activity relationship between nanoparticles’ physicochemical properties and their effects on the immune system to guide safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle–immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15 years of research on the immunotoxicity of engineered nanomaterials.

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“…230 Regarding the distribution across different cancer types ( Fig. 1), patients harboring melanoma were most commonly enrolled in these trials, 186,196,198,205,213,221,223,227,[231][232][233][234] followed by patients with prostate cancer, 206,208,212,215 glioma or glioblastoma (GBM), 185,197,202,219 hepatocellular carcinoma, 204,211,220 non-small cell lung carcinoma (NSCLC), 207,214,230 renal cell carcinoma (RCC), 201,203 esophageal carcinoma, 216,226 and pancreatic ductal adenocarcinoma, 209,217 among others. Of note, only two trials included a wide range of advanced solid tumors refractory to previous treatments.…”

Section: Completed Clinical Trialsmentioning

confidence: 99%

Trial watch: Dendritic cell-based anticancer immunotherapy

et al. 2017

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Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called "maturation cocktail" (typically a combination of pro-inflammatory cytokines and Toll-like receptor agonists), followed by DC reintroduction into patients. DC vaccines have been documented to (re)activate tumor-specific T cells in both preclinical and clinical settings. There is considerable clinical interest in combining DC-based anticancer vaccines with T cell-targeting immunotherapies. This reflects the established capacity of DC-based vaccines to generate a pool of TAA-specific effector T cells and facilitate their infiltration into the tumor bed. In this Trial Watch, we survey the latest trends in the preclinical and clinical development of DC-based anticancer therapeutics. We also highlight how the emergence of immune checkpoint blockers and adoptive T-cell transfer-based approaches has modified the clinical niche for DC-based vaccines within the wide cancer immunotherapy landscape.

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Safety and immunologic correlates of Melanoma GVAX, a GM-CSF secreting allogeneic melanoma cell vaccine administered in the adjuvant setting

Cited by 82 publications

References 60 publications

Vaccination with Irradiated Autologous Tumor Cells Mixed with Irradiated GM-K562 Cells Stimulates Antitumor Immunity and T Lymphocyte Activation in Patients with Recurrent Malignant Glioma

Vaccination with Irradiated Autologous Tumor Cells Mixed with Irradiated GM-K562 Cells Stimulates Antitumor Immunity and T Lymphocyte Activation in Patients with Recurrent Malignant Glioma

Current understanding of interactions between nanoparticles and the immune system

Trial watch: Dendritic cell-based anticancer immunotherapy

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