American Society of Gene & Cell Therapy

American Society of Gene & Cell Therapy

Publisher of Molecular Therapy.  Formerly named Bio-Industry Liaison Committee.

  • In 2010, the ASGCT leadership underwent a comprehensive strategic planning initiative. For more information on ASGCT’s five year strategic plan, please click here.
  • ASGCT implemented two new programs in 2011: the Translational Science Training Course and the NIH Gene Therapy Symposium.

Infectious Diseases

Viral infections can be life threatening in patients who are immune-compromised because they cannot mount an effective immune response. Approaches to protection from infection using gene therapy include T cell-based immunotherapy, stem-cell based therapy, genetic vaccines, and other approaches to genetic blockade of infection. The rationale for use of gene therapy is that most common viral or fungal infections are only life threatening in patients who are immune-compromised because they cannot mount an effective immune response to the virus.

Common causes of inadequate immune responses to viral infections include the Human Immunodeficiency Virus (HIV) which compromises function of immune cells and the necessary immunosuppressive drugs given to patients with an organ or bone marrow transplant.  Both HIV infection and treatments used in transplant patients can cripple the immune response of its victims by killing the helper T cells (CD4+) that help amplify an effective Cytotoxic T Lymphocyte (CTL) immune response against the virally infected cells.

T Cell Based Approaches.  Several approaches that enhance function of T cells with gene transfer using T cells given to patients are in phase I human clinical trials for treatment of HIV, HCV, and EBV infections. For example, T cells are engineered with a novel T cell receptor that recognizes HIV-infected cells.  These engineered T cells will be infused into patients to presumably seek, find, and kill HIV-infected cells. The trial is testing the safety of these cells and ultimately the hypothesis that these cells can slow or halt the progression of the disease.  In a second example, T cells are engineered to produce a material such as an antiviral RNA [See Proc Natl Acad Sci 103: 17323-7, 2006] or an enzyme (zinc finger nuclease) [See Nature Biotech 26: 808-16, 2008] that blocks virus infection. Theoretically, these engineered T cells should not be susceptible to HIV-induced lysis and will help patients maintain a sufficient level of T cells for immune functions.

Cell therapy approaches that transfer abundant T cells specific for several viruses have completed phase I. Some of the therapies are in phase II clinical trials for treatment of transplant patients who have an unrelenting viral infection. The objectives are to gather safety data, feasibility and efficacy data on the transfer of the T cells. As noted, allogeneic hematopoietic stem cell transplant patients are at risk for persistent Adenoviral, CMV, or EBV infections despite standard therapy, and T cells that can kill cells infected with these viruses are being administered to these patients. The patients receive donor-derived T cell lines which are highly virus-specific with minimal alloreactivity, thus minimizing the possibility of graft versus host disease and optimizing the potency and long term presence of the transferred cells. The results of a phase I trial are very encouraging:  the majority of patients with an active CMV, EBV or Adenovirus infection resolved their disease symptoms. The expansion of the viral-specific T cells occurred as the patients began improving [Nature Med. 12:1160-1166. (2006)].  As the lead scientist, Ann Leen, Ph.D. says, “translating basic immunology into a product that affects patients directly is very satisfying.”   To address questions of long-term efficacy, safety, and practicality,  Heslop and colleagues recently reviewed  data from 114 patients who had received infusions of EBV-specificCTLs to preventor treat EBV+ lymphoproliferative disease (LPD) arising after hematopoietic stem cell transplantation.  Toxicity was minimal and none of the 101 patients who received CTL prophylaxisdeveloped EBV+ LPD, while 11 of 13 patients treated with CTLs for biopsy-proven or probable LPD achieved sustained complete remissions. [Blood 115:925-935, 2010].  Development of additional therapies, refinement of these reagents, and further testing are ongoing.