Peptide Vaccination with PR1 Elicits Active T Cell Immunity That Induces Cytogenetic Remission in Acute Myelogenous Leukemia.
Ultima Vez Modificado: 8 de diciembre de 2002
Presenter: Jeffrey J. Molldrem
Presenter's Affiliation: M.D. Anderson
Type of Session: Plenary
- Despite decades of research there are no FDA approved cancer vaccines.
- The concept of tumor immunosurveillance has recently become repopularized with recent research showing that tumor specific antigens do indeed exist.
- There is a known anti-cancer benefit from the graft vs. leukemia effect in allogeneic bone marrow transplant for AML. This led to vaccine research looking to target the same antigens responsible for the graft vs. leukemia effect.
- This study shows the first direct evidence of an anti-leukemia effect from peptide vaccination of leukemia patients.
- Phase I trial of PR1 peptide vaccine. PR1 is an HLA-A2 restricted peptide found only in myeloid cells. T-cell immunity to this protein correlates with remission in CML.
- Patients with relapsed or refractory CML, relapsed AML or MDS were eligible. Patients were ANCA negative at enrollment.
- Endpoints were toxicity; specifically induction of autoimmune vasculitis, and efficacy as measured by induction of immune response.
- 15 patients entered at 3 escalating dose levels of 0.25, 0.5 and 1.0mg given every three weeks for a total of three injections.
- Immune response measured by levels of PR1/HLA-A2 tetramers. Bone marrow obtained prior to first injection and three weeks after final injection to assess disease status.
- No ANCA antibodies and no vasculitis was seen.
- 13 patients had mild pain at the injection site.
- Eight of 15 patients developed an immune response. Of these, 5 obtained a complete hematologic remission and 3 obtained a complete molecular remission.
- Direct activity of PR1-cytotoxic T-lymphocytes (PR1-CTL)against leukemia cells was demonstrated. From one patient, PR1-CTLs showed a 44% lysis of bone marrow cells collected at time of relapse vs 14% lysis of cells collected at time of remission.
- This study provides evidence that a peptide vaccination can induce a targeted immune response against leukemia cells that is capable of inducing remission. Molecular remission is possible in minimal residual disease patients.
- Clinical response in patients correlates with the immune response.
- PR1 specific CTLs persist up to two years following the last vaccination.
- This phase 1 trial provides early in vitro and in vivo evidence that peptide vaccination in ALL patients results in leukemia cell killing. The vaccine also appears to be safe. Though the patient numbers are too low to permit generalizations, the fact that molecular complete remissions were obtained in several patients provides hope that with further phase II and III trials, peptide vaccination may become another valuable weapon in the fight against leukemia.
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