Purpose: This trial evaluated the safety, clinical activity, and immunogenicity of an allogeneic cellular immunotherapy in 55 chemotherapy-naive patients with hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, is a combination of two prostate carcinoma cell lines modified with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene. Experimental Design: HRPC patients with radiologic metastases ( n = 34) or rising prostate-specific antigen (PSA) only ( n = 21) received a prime dose of 500 million cells and 12 boost doses of either 100 million cells (low dose) or 300 million cells (high dose) biweekly for 6 months. End points were changes in PSA, time to progression, and survival. Results: Median survival was 26.2 months (95% confidence interval, 17, 36) in the radiologic group: 34.9 months (8, 57) after treatment with the high dose ( n = 10) of immunotherapy and 24.0 months (11, 35) with the low dose ( n = 24). The median time to bone scan progression in the radiologic group was 5.0 months (2.6, 11.6) with the high dose and 2.8 months (2.8, 5.7) with the low dose. In the rising-PSA group ( n = 21) receiving the low dose, the median time to bone scan progression was 5.9 months (5.6, not reached), and median survival was 37.5 months (29, 56). No dose-limiting or autoimmune toxicities were seen; the most common adverse events were injection site reaction and fatigue. Conclusions: These results suggest that this GM-CSF–secreting, allogeneic cellular immunotherapy is well tolerated and may have clinical activity in patients with metastatic HRPC. Phase 3 trials to confirm these results are under way.

https://clincancerres.aacrjournals.org/content/clincanres/13/13/3883.full.pdf

Granulocyte macrophage colony-stimulating factor--secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer.

The field of cancer vaccines is currently in an active state of preclinical and clinical investigations. Although no therapeutic cancer vaccine has to date been approved by the Food and Drug Administration, several new paradigms are emerging from recent clinical findings both in the use of combination therapy approaches and, perhaps more importantly, in clinical trial design and end point analyses. This article will review recent clinical trials involving several different cancer vaccines from which data are emerging contrasting classic “tumor response” (Response Evaluation Criteria in Solid Tumors) criteria with “patient response” in the manifestation of increased patient survival post-vaccine therapy. Also described are several strategies in which cancer vaccines can be exploited in combination with other agents and therapeutic modalities that are quite unique when compared with “conventional” combination therapies. This is most likely due to the phenomena that ( a ) cancer vaccines initiate a dynamic immune process that can be exploited in subsequent therapies and ( b ) both radiation and certain chemotherapeutic agents have been shown to alter the phenotype of tumor cells as to render them more susceptible to T-cell–mediated killing. Consequently, evidence is emerging from several studies in which patient cohorts who first receive a cancer vaccine (as contrasted with control cohorts) benefit clinically from subsequent therapies.

/pdf/cancer-vaccines-moving-beyond-current-paradigms-2nh1rz5wgs.pdf

Cancer Vaccines: Moving Beyond Current Paradigms

GVAX cancer immunotherapies are composed of whole tumor cells genetically modified to secrete the immune stimulatory cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), and then irradiated to prevent further cell division. Both autologous (patient specific) and allogeneic (non-patient specific) GVAX platforms have been evaluated either as single agents or in combination with other immunomodulatory strategies. Many early-phase clinical trials have now been completed. Results have consistently demonstrated a favorable safety profile manifested primarily by injection site reactions and flu-like symptoms. Consistent evidence of immune activation and clinical activity, including radiologic tumor regressions, has been seen across multiple cancer indications in both early- and late-stage disease. Phase 3 trials evaluating an allogeneic GVAX immunotherapy product in prostate cancer are under way.

GM-CSF gene-modifed cancer cell immunotherapies: of mice and men.

Two randomized clinical trials demonstrated a survival benefit of 20% to 24% with docetaxel-based therapy when compared with survival with mitoxantrone and prednisone after failure of androgen ablation therapy. These studies supported the approval of docetaxel-based therapy for the treatment of metastatic hormone-refractory prostate cancer by the US Food and Drug Administration in May 2005. Clinical trials in hormone-refractory prostate cancer are now focused on building on the survival improvement seen with docetaxel-based therapy. This article presents a summary of some of the more promising treatments and regimens for advanced prostate cancer.

The treatment of hormone-refractory prostate cancer: docetaxel and beyond.

Cancer vaccines constitute a unique therapeutic modality in that they initiate a dynamic process involving the host's immune response. Consequently, (a) repeated doses (vaccinations) over months may be required before patient clinical benefit is observed and (b) there most likely will be a "dynamic balance" between the induction and maintenance of host immune response elements to the vaccinations vs. host/tumor factors that have the potential to diminish those responses. Thus "patient response" in the form of disease stabilization and prolonged survival may be more appropriate to monitor than strictly adhering to "tumor response" in the form of Response Criteria In Solid Tumors (RECIST) criteria. This can be manifested in the form of enhanced patient benefit to subsequent therapies following vaccine therapy. This article will review these phenomena unique to cancer vaccines with emphasis on prostate cancer vaccines as a prototype for vaccine therapy. The unique features of this modality require the consideration of paradigm shifts both in the way cancer vaccine clinical trials are designed and in the way patient benefit is evaluated.

/pdf/paradigm-shifts-in-cancer-vaccine-therapy-1b4su0m0do.pdf

Paradigm Shifts in Cancer Vaccine Therapy

2517 BackgroundA phase 2 study of allogeneic prostate carcinoma cell lines (PC-3 and LNCaP) genetically modified to secrete GM-CSF (GVAX) in 34 met HRPC patients (pts) yielded a median survival of 26 months (Proc ASCO, Vol. 21:183a, 2002). To confirm clinical activity and safety prior to initiation of phase 3 trials a second, expanded Phase 2 study was performed. Methods 80 met HRPC pts were treated for 24 wks. Doses (in millions of cells) ranged from 100 monthly to 500 prime/300 boost bi-weekly. Pts were monitored by bone scans and PSA. Tumor reactive antibodies (ab) were measured by Western blot (WB) of vaccine lysates against pt sera. Bone destruction was monitored by ICTP, a marker of osteoclast activity. Results 80 pts enrolled and completed treatment, and have been followed thus far for a median of 15.0 months with no DLTs observed. Stable or improved bone scans were observed in 43% (31/72) of pts. Stable or decreasing ICTP levels occurred in 62% (34/55) of pts. The median survival has not yet been ...

Clinical and immunologic findings in a phase 2 study of a GM-CSF-secreting prostate cancer cell line vaccine in patients with metastatic hormone-refractory prostate cancer (met HPRC)

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

J. Aimi

Author Tools

Chat about Author

Papers

Clinical and immunologic findings in a phase 2 study of a GM-CSF-secreting prostate cancer cell line vaccine in patients with metastatic hormone-refractory prostate cancer (met HPRC)