Cancer Gene Therapy: Present and Future

Nowadays, there are many Clinical Trials in Cancer are designed for treatment. Several Therapeutic approaches including Small Molecules, Antiangiogenic Compouds, Antibodies, Hematopoietic stem cell transplantation, Cell therapy and Immunotherapy have been investigated at preclinical and clinical Level with the ultimate goal of increasing effect for treatment. However the therapeutic application of Gene therapy should be implemented with new techniques to obtain more achievements in Cancer Treatment by Gene Therapy.

 

 

Gene Therapy was originally intended to treat congenital diseases by introducing the missing gene into appropriate target cells. However as soon as technologies and protocols were developed, it became clear that many acquired diseases could benefit from this therapy modality. Today, more than 60% of ongoing  gene therapy clinical trials are designed to treat cancer  (Edelstein et al., 2007). This high figure is the result of  medical need: despite the fact that several mechanisms of oncogenesis are now understood, cancer is still a major cause of morbidity and mortality worldwide. The high incidence of cancer has encouraged  extensive  scientific  effort  and the high mortality  associated with  advanced disease urges a rapid clinical translation of novel therapeutic approaches with appropriate assessment  of the risk/benefit ratio.

 

      In this scenario, several therapeutic approaches, alternative  to gene therapy , including small molecules, antiangiogenic  compounds, antibodies, hematopoietic  stem cell transplantation, cell therapy and immunotherapy have been investigated at preclinical and clinical levels with the ultimate goal of increasing the rate of response obtained  by conventional chemoradiotherapy. The majority of these approaches produced  clinical success to various degrees at least  in selected tumors. On the other hand, the initial clinical experience with biodrugs, cell therapy, and small molecules revealed their limitations. Several small molecules are highly active but only in selected subsets of patients affected by a specific disease. Adoptive  cellular immunotherapy is highly active but can be offered only in the small subset of cancer patients from whom tumor specific lymphocytes can be identified  and expanded in vitro. Allogeneic  stem cell transplantation is  high effective against several hematologic malignancies but is affected by a high rate of  transplant-related mortality, largely due to graft versus host diseas. The high rate of clinical response to antibodies is often transient.

 

The transfer and expression of genes,  the common motif of a wide range of  therapeutic approaches included in the definition of gene therapy, have tremendous potential to overcome the limitations of standard and more innovative drugs. To move from the pioneering stage to a mature clinical phase, gene therapy is today required not only to compete with but often to synergize and sometimes to enable established and novel therapeutic platforms.

 

      On the basis of these considerations, we reasoned  that a series of reviews covering topics related to the therapeutic application of gene therapy  to cancer should be implemented. In the next four issues of Human Gene Therapy, we will learn how gene transfer technology allow us to overcome  the intrinsic limitations of cancer immunotherapy by producing for every candidate patient virtually infinite number of tumor specific lymphocytes by transferring tumors specific T cell receptor gene into the patient’s cells. In addition the review series will focus on how the specificity of antibodies can be exploited  to obtain long-term clinical responses by transferring chimeric  antigen receptor genes into human lymphocytes, and on the advantages of introducing a gene encoding an entire antigen  into human dendritic cells to prepare potent cancer vaccines. We will also explore the complex activity of oncolytic vectors in cancer cell, the tumor environment, and innate and adaptive immunity and learn how the transfer of suicide gene into donor lymphocytes enable hiplo-indentical stem cell transplantation by turning its side effects. Finally, we will explore the potential of gene transfer to inhibit tumor angiogenesis and discuss the advantages offered  by gene therapy as compared with antibodies and small molecules in treating  head and neck cancer.

 

       Undeniably, gene therapy is limited by its high technological complexity and subsequent cost. This is a high relevant limitation for a novel therapeutic approach still in need of support from the proper business models. This challenge needs to be met and will be faced  by appropriate clinical trials and competitive clinical results.

 

 

 

 

 

 

 

 

 

Source: Chiara Bnini and Bernd Gansbacher.

 

 

 

HUMAN GENE THERAPY 20:1100 (October 2009)

 

Mary Ann Liebert. Inc

 

DOI:10. 1089/hum 2009. 911