Redirected High Affinity Gag‐Specific Autologous T Cells for HIV Gene Therapy
| Status: | Completed |
|---|---|
| Conditions: | HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 12/15/2017 |
| Start Date: | November 2009 |
| End Date: | January 2014 |
A Pilot, Open Label, Multi Arm, Single Ctr Study to Evaluate Safety & Tolerability of Escalating Doses of Autologous T Cells Modified With Lentiviral Vectors Expressing High Affinity Gag-specific TCRS in HLA-A02 Patients With HIV
This research study is being carried out to study a new way to possibly treat HIV. T‐cells
are one of the white blood cells used by the body to fight HIV. CD8 T‐cells are a type of
T‐cell used by the body to detect and kill cells which have been infected by foreign viruses
or organisms, including the HIV virus. CD8 T‐cells must identify the HIV virus in order to
kill it. Because HIV is constantly changing the way it looks to the CD8 T‐cells, some of the
HIV virus escapes detection and is not killed by the CD8 T‐cells.
This research study uses a T cell receptor (TCR) protein specific for HIV (SL9 TCR) and adds
it to the CD8 T‐cells in the laboratory in order to help the CD8 T‐cells recognize the
constantly changing HIV virus and make it able to fight HIV more efficiently. TCR stands for
T cell receptor. TCRs are found on the surface of T cells and allow the T cells to recognize
other cells. Laboratory studies have shown that when CD8 T‐cells are modified with SL9 TCRs,
they kill cells that are infected with HIV better than normal CD8 T‐cells can. On the basis
of these laboratory results, there is the potential that SL9 TCRs may work in people infected
with HIV and improve their immune system by killing HIV infected cells and thus may help
control HIV infection.
Two different SL9 TCRs will be tested in this study, WT‐gag‐TCR and α/6‐gag‐TCR. Two
different types of SL9 TCRs are being used in this research study because the laboratory
studies suggest that the different SL9 TCRs will function differently depending on the amount
of virus in your body. A goal of this clinical study is to test the effects of infusions of
either SL9 TCR in the presence or absence of a viral load.
All subjects who receive WT‐gag‐TCR or the α/6‐gag‐TCR T cells will be enrolled in a Long
Term Follow up study to monitor subjects. Subjects will be followed every 6 months for five
years following the 1st infusion of the T cells. If the WT‐gag‐TCR or the α/6‐gag‐TCR T cells
are no longer found in the blood after five years, then subjects will be contacted yearly for
the next 10 years. If the WT‐gag‐TCR or the α/6‐gag‐TCR T cells are found in the blood at
five years after the 1st infusion of T cells, then the subjects will continue to be seen once
a year until the WT‐gag‐TCR or the α/6‐gag‐TCR T cells are no longer found in the blood for a
maximum of 15 years.
are one of the white blood cells used by the body to fight HIV. CD8 T‐cells are a type of
T‐cell used by the body to detect and kill cells which have been infected by foreign viruses
or organisms, including the HIV virus. CD8 T‐cells must identify the HIV virus in order to
kill it. Because HIV is constantly changing the way it looks to the CD8 T‐cells, some of the
HIV virus escapes detection and is not killed by the CD8 T‐cells.
This research study uses a T cell receptor (TCR) protein specific for HIV (SL9 TCR) and adds
it to the CD8 T‐cells in the laboratory in order to help the CD8 T‐cells recognize the
constantly changing HIV virus and make it able to fight HIV more efficiently. TCR stands for
T cell receptor. TCRs are found on the surface of T cells and allow the T cells to recognize
other cells. Laboratory studies have shown that when CD8 T‐cells are modified with SL9 TCRs,
they kill cells that are infected with HIV better than normal CD8 T‐cells can. On the basis
of these laboratory results, there is the potential that SL9 TCRs may work in people infected
with HIV and improve their immune system by killing HIV infected cells and thus may help
control HIV infection.
Two different SL9 TCRs will be tested in this study, WT‐gag‐TCR and α/6‐gag‐TCR. Two
different types of SL9 TCRs are being used in this research study because the laboratory
studies suggest that the different SL9 TCRs will function differently depending on the amount
of virus in your body. A goal of this clinical study is to test the effects of infusions of
either SL9 TCR in the presence or absence of a viral load.
All subjects who receive WT‐gag‐TCR or the α/6‐gag‐TCR T cells will be enrolled in a Long
Term Follow up study to monitor subjects. Subjects will be followed every 6 months for five
years following the 1st infusion of the T cells. If the WT‐gag‐TCR or the α/6‐gag‐TCR T cells
are no longer found in the blood after five years, then subjects will be contacted yearly for
the next 10 years. If the WT‐gag‐TCR or the α/6‐gag‐TCR T cells are found in the blood at
five years after the 1st infusion of T cells, then the subjects will continue to be seen once
a year until the WT‐gag‐TCR or the α/6‐gag‐TCR T cells are no longer found in the blood for a
maximum of 15 years.
See Above
Inclusion Criteria:
- Age 18 years or older
- Karnofsky Performance of 80 or higher
- HLA-A2 Positive
- Chronic HIV-1 infection
- On stable HAART regimen (with no changes within 4 weeks of study entry)
- Willing to undergo a limited treatment interruption of antiretroviral medication
- CD4+ T cell count ≥450 cells/mm3
- Documented CD4 nadir of ≥200 cells/mm3
- Undetectable HIV-1 RNA
- ARMS 1 and 2 only, at least a singe documented historic viral load set point reading
- Lab Values: Hgb≥10 males; ≥9.5 females ; ANC≥1000/mm3 ; Platelets≥1000,000/mm3 ;
Creatinine≤1.5 mg/dL ; AST, ALT ≤ 2.5xULN
Exclusion Criteria:
- Current or prior AIDS diagnosis
- Previous participation in any gene therapy using an integrating vector (subjects
treated with Placebo will not be excluded)
- History of cancer or malignancy (allowed to have successfully treated basal cell or
squamous cell carcinoma of the skin)
- Have history or current exam indicative of active or unstable cardiac disease or
hemodynamic instability
- Have history or current exam indicative of bleeding diathesis
- Previous treatment with any HIV experimental vaccine within 6 months prior to
screening
- Use of chronic corticosteroids, hydroxyurea or immunomodulating agents such as IL2,
interferon alpha, interferon gamma, granulocyte colony stimulating factors within 30
days prior to study entry (inhaled steroids are not exclusionary)
- Currently breast feeding, pregnant or unwilling to use acceptable methods of birth
control
- Use of aspirin, dipyridamole, warfarin or any other medication that is likely to
affect platelet function or other aspects of blood coagulation during the 2 week
period prior to leukapheresis
- Active drug or alcohol use/dependence
- Serious illness requiring systemic treatment and/or hospitalization within 30 days
prior to study entry
- Receipt of a vaccination within 30 days prior to study entry
- Have a known allergy or hypersensitivity to human serum albumin, DMSO or Dextran 40
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