Know Cancer

forgot password

Gene Therapy for AIDS Using Retroviral Mediated Gene Transfer to Deliver HIV-1 Anti-Sense TAR and Transdominant Rev Protein Genes to Syngeneic Lymphocytes in HIV-1 Infected Identical Twins

Phase 1
Not Enrolling
Acquired Immunodeficiency Syndrome, HIV Infection, Kaposi's Sarcoma

Thank you

Trial Information

Gene Therapy for AIDS Using Retroviral Mediated Gene Transfer to Deliver HIV-1 Anti-Sense TAR and Transdominant Rev Protein Genes to Syngeneic Lymphocytes in HIV-1 Infected Identical Twins

This phase I/II pilot study will evaluate the safety, relative survival, and potential
efficacy of infusions of activated, genetically engineered, syngeneic CD4+ T lymphocytes
obtained from HIV-1 seronegative identical twins. T cells from each seronegative twin will
be obtained by apheresis, enriched for CD4+ cells, induced to polyclonal proliferation with
anti-CD3 and rIL-2 stimulation, divided into aliquots which will then be individually
transduced with a control retroviral vector and up to two additional retroviral vectors
containing potentially therapeutic genes (antisense TAR and/or transdominant Rev). These
engineered T cell populations will be expanded 10-1,000 fold in numbers during 1-2 weeks of
culture, and then will be infused into the seropositive twins. The relative survival of the
uniquely engineered T cell populations will be monitored by vector-specific PCR, while the
recipients' functional immune status is monitored by standard in vitro and in vivo testing
protocols. A total of up to 4 cycles of treatment may be given using identical or different
combinations of control and anti-HIV-1 retroviral vectors.

Inclusion Criteria


- An identical twin pair, one of whom is seropositive for HIV-1, the other twin
seronegative, by standard ELISA and Western blot testing.

- Patients with Kaposi's sarcoma limited to the skin and/or mucous membranes are
eligible for this study, but must not have received any systemic therapy for

- KS within 4 weeks prior to entry. The diagnosis of KS must have been confirmed by

- Free from serious psychological or emotional illness and able to provide written
informed consent.

- Anticipated survival greater than 3 months.

- 18 years of age or older.

- Treatment with FDA-approved and/or expanded access antiretroviral agent(s) for
patients with baseline CD4 counts below 500 cells/mm(3). Patients with baseline CD4
counts above 500 cells/mm(3) are eligible to receive cell therapy on this protocol,
but must be treated with antiretroviral therapy if evidence of significant and
persistent viral activation occurs in association with a cell infusion. "Significant
and persistent viral activation" is defined as a 50 percent or greater increase above
baseline in any virologic parameter for at least 2 consecutive weeks.

- Recipient's CD4 count greater than 50 cells/mm(3).

- Recipient and Donor willing to have samples stored and undergo HLA testing.

EXCLUSION CRITERIA (Donor and Recipient):

- Lymphomas.

- Unwillingness to comply with current NIH Clinical Center guidelines concerning
appropriate notification of all current sexual partners of an individual regarding
his or her HIV-1 positive sero-status and the risk of transmission of HIV-1

- Recent history of substance abuse unless evidence is provided of an ongoing
therapeutic intervention (i.e. medical therapy or counseling) to control such abuse.

- Pregnant at entry or unwillingness to practice barrier birth control or abstinence
during the study.

- No experimental therapy within 4 weeks of study participation. Antiretroviral agents
available on an FDA-sanctioned, expanded access basis are permitted.


- Untreated or inadequately treated medical condition (e.g., cardiopulmonary disease,
acute infection) which, in the judgement of the Principal Investigator, precludes

- Serologic positivity for Epstein Barr virus, Cytomegalovirus, Hepatitis B or
Hepatitis C, if and only if the recipient twin tests seronegative for the
corresponding virus.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

March 1996

Completion Date:

March 2002

Related Keywords:

  • Acquired Immunodeficiency Syndrome
  • HIV Infection
  • Kaposi's Sarcoma
  • Intracellular Immunization
  • Immune Based Therapy
  • Ex Vivo Cell Processing
  • Identical Twins
  • Kaposi's Sarcoma
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
  • Immunologic Deficiency Syndromes
  • Sarcoma, Kaposi
  • Sarcoma



National Human Genome Research Institute (NHGRI) Bethesda, Maryland  20892