Category Archives: Immunotherapy

C 032: CHEMO-IMMUNOTHERAPY FOR CANCER: A RATIONAL SCIENTIFIC AND THERAPEUTIC

J Pharm Pharmacogn Res 2(Suppl. 1): S98, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

C 032: CHEMO-IMMUNOTHERAPY FOR CANCER: A RATIONAL SCIENTIFIC AND THERAPEUTIC

Soriano García JL.

Clinical Oncology Service. Ameijeiras´Hospital, La Habana, Cuba.
Abstract

Cancer therapy is designed to specifically integrate distinct treatment modalities in the most effective way to achieve the highest cure rate. Surgery and radiation therapies are used for loco regional disease control, whereas systemic therapies are used to treat micrometastatic or widespread metastatic cancers and hematologic malignancies. While systemic therapies have historically been given after local measures have been undertaken to remove the primary tumor, they are increasingly used prior to definitive local treatment both to achieve systemic disease control earlier and to evaluate the responsiveness of the tumor to treatment. Regardless of the timing in relation to local therapy, these systemic treatments—chemotherapy, endocrine therapy, small molecular targeted therapies and monoclonal antibodies–are designed to decrease the likelihood of relapse due to micrometastatic disease. Cancer chemotherapy drugs have long been considered immune suppressive. However, more recent data indicate that some cytotoxic drugs effectively treat cancer in part by facilitating an immune response to the tumor when given at the standard dose and schedule. These drugs induce a form of tumor cell death that is immunologically active, thereby inducing an adaptive immune response specific for the tumor. In addition, cancer chemotherapy drugs can promote tumor immunity through ancillary and largely unappreciated immunologic effects on both the malignant and normal host cells present within the tumor microenvironment. These more subtle immunomodulatory effects are dependent on the drug itself, its dose, and its schedule in relation to an immune-based intervention. A detailed understanding of the cellular and molecular basis of interactions between chemotherapy drugs and the immune system is essential for devising the optimal strategy for integrating new immunebased therapies into the standard of care for various cancers, resulting in the greatest long-term clinical benefit for cancer patients. Current data suggest that combining chemotherapy in standard and novel ways with immune-based interventions will have great potential for optimizing the clinical outcomes of cancer patients. A new era of effectively harnessing the immune system to treat and prevent cancer has begun. These early successes have ledto heightened interest and activity in developing new strategies for tipping the balance of the hosttumor interaction toward definitive tumor rejection. It is clear that strategically integrating immune-based therapies with standard cancer treatment modalities, in particular chemotherapy drugs, has the potential to reengineer the overall host milieu and the local tumor microenvironment to disrupt pathways of immune tolerance and suppression (to understand the differences in immunobiology between the distinct histologies and biologic subtypes of cancer will be critical for identifying the optimal antigen and/or immunologic pathway to target for a particular cancer or to dissect mechanisms of intrinsic and adaptive therapeutic resistance to immune-based treatments will be critical for ensuring clinical success). In designing combination immunotherapy regimens, clinical investigators should consider how chemotherapy impacts the immune system in order to guide the dose and schedule for integrating chemotherapy and immunotherapy. In particular, systematically defining the optimal drug dose and timing in relation to immune-based therapy in early-phase clinical studies is imperative for the design of phase II and III clinical trials with a higher
likelihood of clinical success. Finally, delineating the impact of established cancer drugs and standard cancer treatment modalities on the immune system and on tumor immuno biology itself will be critical for the most effective integration of immune-based cancer therapy into state-of-the art multimodality cancer care.

IMMUNOTHERAPY AND COMPLEXITY: OVERCOMING THE BARRIERS FOR THE CONTROL OF ADVANCED CANCER

J Pharm Pharmacogn Res 2(Suppl. 1): S1, 2014

Special supplement with the abstract book of LATINFARMA 2013

Plenary Lecture

PL 002: IMMUNOTHERAPY AND COMPLEXITY: OVERCOMING THE BARRIERS FOR THE CONTROL OF ADVANCED CANCER

Lage Dávila A.

Director General, Centro de Inmunología Molecular, Cuba.
Abstract

Age-adjusted cancer mortality rates are showing a slow, but clear trend to decline in some countries. However, such decline is mostly due to reduction in tobacco smoking and to earlier diagnosis of some tumors. Long term control of advanced cancer continue to be a goal very hard to attain: Survival gains over the last three decades for many tumors are measured in months, not years. Four major barriers prevent a faster progress: the complexity of networks for the control of cell proliferation; the heterogeneity of cancer cells; the mutation rate; and our genome-environment mismatch. They challenge the classic pharmacology paradigm of “one molecular target/one specific drug¨. Targeted therapy, the most recent acquisition for the treatment of advanced cancer, together with its impressive short term effects,
illustrate the limitation of the strategy, due to the fast appearance of resistance. The complexity of regulatory networks will demand simultaneous intervention on several molecular targets and capacity to handle the ¨dual effects¨. Patient to patient heterogeneity and cell to cell heterogeneity will demand personalized medicine and clinical trials in smaller patient niches. Mutation rates will need the mobilization of biologic mechanisms, such as the immune system, which could evolve together with the tumor. Finally these mechanisms should act in a genetic background which has not been selected by evolution for protecting health in the post-reproductive period of human life. Neither classic screening strategies of pharmacology, nor the current regulatory context for drug development are well suited for facing these challenges. Biotechnology drugs offer the possibility of innovative approaches. Recent evidences related to the effect of monoclonal antibodies and therapeutic vaccines, and data related to the control of the immune response, epitope spreading, pathways of apoptosis, oncogene addiction and immuno-senescence point out the possibility to stepwise transform the clinical course of advanced cancer into that of a chronic disease compatible of years of quality life.