Margaret A. Fischl, M.D., F.A.C.P.
Professor of Medicine
Description of Research
Dr. Fischl’s laboratory focuses on prevention and treatment research for HIV/AIDS in men, women and children; assessment of HIV vaccines and adjuvants; mucosal and innate immunity implication of the prevention and attainment of HIV-1 infection; as well as Kaposi’s sarcoma and HPV.
- Assessed (through collaboration) a novel monoclonal antibody to CCR5—PRO 140—a possible new novel HIV-1 entry inhibitor and the assessment of co-receptor usage.
- Completed PRO 140 1302, a Phase IB, double-blind, randomized, dose-cohort escalation study of intravenous PRO 140 or placebo in adult patients with HIV-1 infection.
- Assessed (through collaboration) the immunologic changes induced by rhIL-7 administration in HIV-infected patients currently receiving a stable antiretroviral regimen. In A5214, a Phase I, randomized, placebo-controlled, double-blind study evaluating the safety of subcutaneous single dose Interleukin-7 in HIV-1-infected subjects who are receiving antiretroviral treatment (the first study to examine the effect of rhIL-7 in HIV-infected patients), Dr. Fischl found that rhIL-7 induced T-cell proliferation, as measured by a novel intracellular Ki67 assay, and increased CD4/CD8 cell counts. These observations suggest that co-administration of rhIL-7 with combination antiretroviral therapy may greatly increase the effectiveness of the treatment, especially in those patients (about 30 percent) who have reduced immune recovery and are thus susceptible to disease progression. Based on the A5214 findings, a subsequent randomized clinical trial to test the effectiveness of rhIL-7 will be conducted.
Selected Cancer-Related Publications
- Lévy Y, Sereti I, Tambussi G, Routy JP, Lelièvre JD, Delfraissy JF, Molina JM, Fischl M, Goujard C, Rodriguez B, Rouzioux C, Avettand-Fenoël V, Croughs T, Beq S, Morre M, Poulin JF, Sekaly RP, Thiebaut R, Lederman MM. Effects of Recombinant Human Interleukin 7 on T-Cell Recovery and Thymic Output in HIV-Infected Patients Receiving Antiretroviral Therapy: Results of a Phase I/IIa Randomized, Placebo-Controlled, Multicenter Study. Clin Infect Dis 55:291-300, 2012. Read more »
- Niu L, Termini JM, Kanagavelu SK, Gupta S, Rolland MM, Kulkarni V, Pavlakis GN, Felber BK, Mullins JI, Fischl Ma, Stone GW. Preclinical evaluation of HIV-1 therapeutic ex vivo dendritic cell vaccines expressing consensus Gag antigens and conserved Gag epitopes. Vaccine 29:2110-9, 2011. Read more »
- Ross LL, Weinberg WG, DeJesus E, Fischl Ma, Horton JH, Pappa KA, Lancaster CT, Pakes GE, Smith KY. Impact of low abundance HIV variants on response to ritonavir-boosted atazanavir or fosamprenavir given once daily with tenofovir/emtricitabine in antiretroviral-naive HIV-infected patients. AIDS Res Hum Retroviruses 26:407-17, 2010. Read more »
- Sachdeva M, Fischl Ma, Pahwa R, Sachdeva N, Pahwa S. Immune Exhaustion Occurs Concomitantly With Immune Activation and Decrease in Regulatory T Cells in Viremic Chronically HIV-1-Infected Patients. J Acquir Immune Defic Syndr 54:447-54,2010 Read more »
- Sereti I, Dunham RM, Spritzler J, Aga E, Proschan MA, Medvik K, Battaglia CA, Landay AL, Pahwa S, Fischl Ma, Asmuth DM, Tenorio AR, Altman JD, Fox L, Moir S, Malaspina A, Morre M, Buffet R, Silvestri G, Lederman MM. IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Blood 113:6304-6314, 2009. Read more »