WT1 Peptides

[Guest guest]

Study and backgrounder. ~ Karl

=A Phase I Study of WT1 Peptides to Induce Anti-Leukemia Immune Responses

Following Autologous or Allogeneic Transplantation for AML, CmML, ALL, MDS,

and B Cell Malignancies (WT-1)

This study is currently recruiting participants.

Verified by Duke University, May 2008

Sponsored by: Duke University

Information provided by:Duke University

ClinicalTrials.gov Identifier:NCT00672152

The purpose of this study is to determine the safety and effectiveness of

administering WT1 cancer peptides. Cancer peptides are short pieces of

protein that are made in a laboratory to be like the peptides that can be

found in cancer.

These peptides are intended to be given as a " vaccine " to activate the

immune cells in a person to attack his/her cancer. These peptides are mixed

with an oily substance called Montanide ISA-51 and a white cell growth

factor called GM-CSF which may help make the immune response stronger.

Study details: http://clinicaltrials.gov/ct2/show/NCT00672152

Background on WT1 cancer peptides:

http://www.thescientificworld.com/TSW/toc/TSWJ_ArticleLanding.asp?jid=0 & ArticleI\

d=2643 & sortby=name

Abstract

Wild-type Wilms' tumor gene WT1 is expressed at a high level in

hematopoietic malignancies including acute leukemia, chronic myelogenous

leukemia, and myelodysplastic syndromes, as well as in various kinds of

solid cancers.

Human cytotoxic T lymphocytes (CTLs), which could specifically lyse

WT1-expressing tumor cells with HLA class I restriction, were generated in

vitro. It was also demonstrated that mice immunized with the WT1 peptide

rejected challenges by WT1-expressing cancer cells and survived with no

signs of autoaggression to normal organs that physiologically expressed WT1.

Furthermore, we and others detected IgM and IgG WT1 antibodies in patients

with hematopoietic malignancies, indicating that the WT1 protein was highly

immunogenic, and that immunoglobulin class-switch-inducing, WT1-specific,

cellular immune responses were elicited in these patients.

CD8+ WT1-specific CTLs were also detected in peripheral blood or

tumor-draining lymph nodes of cancer patients. These results provided us

with the rationale for elicitation of CTL responses targeting the WT1

product for cancer immunotherapy. On the basis of these findings, we

performed a phase I clinical trial of a WT1 peptide cancer vaccine for the

patients with malignant neoplasms.

These results strongly suggested that the WT1 peptide cancer vaccine had

efficacy in the clinical setting because clinical responses, including

reduction of leukemic blast cells or regression of tumor masses, were

observed after the WT1 vaccination in patients with hematopoietic

malignancies or solid cancers.

The power of a tumor-associated-antigen (TAA)-derived cancer vaccine may be

enhanced in combination with stronger adjuvants, helper peptide,

molecular-target-based drugs, or some chemotherapy drugs, such as

gemcitabine, which has been revealed to suppress regulartory T-cell

function.

In contrast, reduction of WT1 peptide dose may be needed for the treatment

of patients with hematological stem cell diseases, because rapid and strong

destruction of malignant cell-sustained hematopoiesis before recovery of

normal hematopoiesis may lead to pancytopenia in these patients.