Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PROCROP (Professional cross-priming for ovary and prostate cancer)

Teaser

Cancer immunotherapy has emerged as a potent therapeutic tool against many cancer types over the results observed in the treatment of patients with the so-called “immune checkpoint blockers”. PROCROP is a European initiative aimed at the development of a novel...

Summary

Cancer immunotherapy has emerged as a potent therapeutic tool against many cancer types over the results observed in the treatment of patients with the so-called “immune checkpoint blockers”. PROCROP is a European initiative aimed at the development of a novel immunotherapeutic approach for metastasic ovarian and castration resistant prostate cancer. The fact that residual tumor cells frequently remain following surgery makes it suitable for testing new approaches at clinical level. PROCROP intends to explore the potential of a particular subset of antigen-presenting cells (XP-DCs) to generate personalized cancer vaccines. Extensive research in animal models and cell cultures has attributed a fundamental role to XP DCs in promoting specific immune responses. In a multicentric coordinated effort PROCROP will develop vaccines by isolation of XP DCs from the blood of ovary and prostate cancer patients. For this purpose 6 clinical and academic institutions and an industrial partner with proven expertise in the field have joined forces in the pursuit of a novel immunotherapeutic approach. XP DCs isolated from blood will be loaded with tumor material from surgical resections, activated and injected to the patients to promote immune responses against remaining tumor cells in ovary/prostate cancer patients. For this, PROCROP will explore the use of these vaccines in preclinical models, develop and optimize a cellular product based on laboratory isolation of these cell subsets from patients’ blood and perform two clinical trials to demonstrate immunogenicity and therapeutic efficacy of XP DC vaccination.

Work performed

Since the beginning of the project preclinical data have shown the relevance of XP DC in immune response against cancer in different mice models and experimental settings. Most efforts have focused on the development of the isolation equipment to obtain the XP DCs from blood and study of their feasibility for clinical trials. We have developed a technique to recover sufficient yields of highly purified XP DCs. The cell-isolation product and the instrumentation setup are almost complete and the release criteria have been agreed by all partners. Preclinical research has produced a similar vaccine in mice models understanding the optimal conditions for vaccination. Work is ongoing to define the best protocol to ensure survival, antigen load and optimal activation of cells before starting patient vaccination in clinical trials. This information is also necessary to prepare a safety and efficacy dossier soon to be submitted to regulatory authorities in three European countries.

Final results

DC vaccination has proven to be a potential therapeutic approach against cancer in clinical trials around the world being able to promote immune responses against different tumors. PROCROP has focused on the cancer patients that can more easily benefit from a DC vaccination therapy to test a treatment based on a minority DC subset so far ignored for the use in vaccination strategies, and recently shown to be of key importance in the immune response against tumors. This population is represented in very low numbers in human blood, and the ability to purify big highly-pure yields of these cells from patients is a major achievement accomplished by the consortium. The use of these cells for vaccination strategies seems feasible according to the data obtained by PROCROP. This is a major advancement in autologous cellular therapy since these cells represent less than a 0.05% of total white cells in human blood. Despite the limited number of cells that can be obtained, sufficient numbers for vaccination studies are feasible and the viability and activity tested so far seems optimal to induce good responses against tumor antigens. Therefore the use of this novel approach of DC vaccination in clinical trials is predicted to be more efficient in promoting immune responses against tumors than previous dendritic cell vaccines and is expected to provide benefits to the ovary and prostate cancer patients enrolled in the clinical trials.
Impact
•New therapeutic strategy, adapted to the needs of men (prostate) and women (ovary), with potential to benefit the clinical practice for these chronic, highly prevalent and deadly diseases.
•Contribute to improve the therapeutic outcome of major chronic, non-infectious health issues with significant impact on individual patients and health care systems in Europe. Prolonging life expectancy increasing the percentage of disease-free survival in postsurgical patients is extremely important to reduce morbi-mortality. This is a unique opportunity for European researchers to pioneer a treatment at the cutting-edge of tumour immunotherapy, leveraging on scientific knowledge first attained in Europe, resulting in unique product development capabilities.
•A prototype clinical-grade cell separation and culture product to be commercially exploited in the preparation of a therapeutic vaccine. This will be marketed by European company Miltenyi, owning IP on the cellular selection technologies and on the selecting mAb. The new PRODIGYTM instrument, allows robotic manipulation in closed systems and standardization for larger trials. Its introduction in clinical centres will demonstrate the benefit over the standard of care. This is a major strength of PROCROP; Miltenyi has an extensive portfolio of products in the market and is a world leader in the markets of preclinical biotechnology and cell therapy.
•Clinical validation for safety and pharmacodynamics (immunodynamics mode of action) of a novel cell therapy product for prevalent forms of genitourinary cancer afflicting males and females, with current unsatisfactory treatment.
•Survival benefit for prostate and ovary cancer patients based on increased immune responses elicited by professional cross-priming DCs. This is an improvement over current DCs products. PROCROP will reap previous basic and clinical research on DC for clinical efficacy. The setting will be tested in terms of decreasing postsurgical relapses as major accomplishment.
•Knowledge and publications in international high impact-factor journals (in cancer, immunology and immunotherapy) on the function of human CD141+ and their mouse analogues to elicit CTL against cancer antigens and therapeutic effects against preclinical models of prostate cancer. These results will optimize final dossiers of PROCROP trials and guide researchers in subsequent endeavours. Reports of clinical outcomes with immunomonitoring results should bring about articles in top clinical journals.
•Optimisation and

Website & more info

More info: http://www.procrop.eu.