Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients.
OBJECTIVE
The telomerase reverse transcriptase hTERT is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes (CTL). We have previously shown that vaccination of cancer patients against hTERT induces functional anti-tumor CTL in vivo, but it is not known whether hTERT vaccination harms normal cells expressing the enzyme, especially hematopoietic stem cells and progenitors.


METHODS
We employed colony-forming cell (CFC) assays, long-term in vitro cultures, and nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulation studies to evaluate the effects of hTERT vaccination on hematopoietic progenitors and stem cells in cancer patients following treatment.


RESULTS
Using bone marrow samples obtained from cancer patients before and after vaccination, we found that there was no significant decline in the frequency of granulocyte, macrophage or erythroid CFCs using CFC assays or long-term in vitro cultures. In NOD/SCID mice, human hematopoietic reconstitution was easily detected, without quantitative or qualitative differences between pre- and postvaccine samples.


CONCLUSIONS
These findings suggest that induction of tumor-lytic hTERT-specific T cells in vivo by vaccination does not result in a detectable decline in hematopoietic potential despite the expression of hTERT and major histocompatibility complex class I in bone marrow progenitors and stem cells. Thus, even for self-antigens such as telomerase, tumor immunity does not necessarily involve autoimmunity in normal tissues that share the target.
Danet-Desnoyers
Gwenn-Aël H
GA
Division of Hematology-Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Luongo
Jennifer L
JL
Bonnet
Dominique A
DA
Domchek
Susan M
SM
Vonderheide
Robert H
RH
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D001943:Breast Neoplasms / Q000628:therapy; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000628:therapy; D013234:Stem Cells / Q000187:drug effects*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D019098:Telomerase / Q000276:immunology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D019098:Telomerase