Riddell SR, Walter BA, Gilbert M, Corey L, Greenberg PD; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1994 Oct 4-7; 273.

Fred Hutchinson Cancer Research Center, Seattle, WA.

Deficiencies of virus-specific CD8+ class I MHC restricted CTL are responsible for the progression of CMV infection in immunocompromised hosts and may contribute to the progression of HIV infection and HIV infected individuals. A study in our lab of 14 bone marrow transplant (BMT) recipients has shown that the adoptive transfer of clonally derived CD8+ CMV- specific T cells, isolated from the marrow donor and propagated in vitro to cell doses of 1.5 X 10(9)/m2, safely restores protective levels of CD8+ CTL. Using the unique alpha beta T cell receptor gene rearrangements as a marker, transferred CTL can be detected in vivo for greater than 3 months. The adoptive transfer of autologous in vitro expanded CD8+ HIV-specific CTL may augment host immunity to HIV in HIV infected individuals. This approach is now being studied in 15 HIV seropositive individuals with CD4+ T cell counts of 200 - 500/mm3. Because of the nature of host cells infected with HIV which includes microglial cells in the CNS, there is the potential for toxicity developing if transferred CTL provoke an inflammatory response. Thus, CD8+ HIV gag-specific CTL are genetically modified by retrovirus mediated gene transfer to introduce a marker/suicide gene which encodes hygromycin phosphotransferase (Hy) and herpes virus thymidine kinase (TK). HyTK provides a means of selecting transduced T cell clones in vitro and monitoring their survival and migration in vivo. Moreover, transduced CTL are rendered sensitive to ganciclovir and can potentially be ablated in vivo if toxicity occurs at high cell doses. Total cell doses of 5 X 10(9)/m2 are being infused and the patients are monitored for toxicity, changes in immune function, anti viral effects, and the evolution of escape mutants. The development of an effective suicide gene strategy will facilitate the future evaluation of CD8+ CTL rendered helper independent by gene transfer techniques for the immunotherapy of HIV.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Adoptive Transfer
• Antigens, CD4
• Antigens, CD8
• Bone Marrow Transplantation
• CD4-Positive T-Lymphocytes
• Clone Cells
• Cytomegalovirus Infections
• HIV Infections
• HIV Seropositivity
• Humans
• Immunotherapy, Adoptive
• In Vitro
• Receptors, Antigen, T-Cell, alpha-beta
• T-Lymphocytes
• T-Lymphocytes, Cytotoxic
• immunology
• surgery
• transplantation

Other ID:

• 95921013

UI: 102213953

From Meeting Abstracts