PMID- 18544677
OWN - NLM
STAT- MEDLINE
DCOM- 20080930
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 112
IP  - 5
DP  - 2008 Sep 1
TI  - Targeting a single mismatched minor histocompatibility antigen with 
      tumor-restricted expression eradicates human solid tumors.
PG  - 1844-52
LID - 10.1182/blood-2007-11-125492 [doi]
AB  - Regressions of metastatic solid tumors after allogeneic human leukocyte antigen 
      (HLA)-matched stem cell transplantation (SCT) are often associated with 
      detrimental graft-versus-host disease (GVHD). The graft-versus-host reaction of 
      the HLA-matched donor is directed mainly against the multiple mismatched minor 
      histocompatibility antigens (mHags) of the patient. mHags are strong 
      HLA-restricted alloantigens with differential tissue distribution. Ubiquitously 
      expressed mHags are the prime in situ targets of GVHD. The mHag HA-1 is 
      hematopoiesis restricted, but displays additionally an aberrant expression on 
      solid tumors. Thus, HA-1 might be an excellent target to boost the anti-solid 
      tumor effect of allogeneic SCT without inducing severe GVHD. Here, we show that 
      cytotoxic T lymphocytes (CTLs) solely targeting the human mHag HA-1 are capable 
      of eradicating 3-dimensional human solid tumors in a highly mHag-specific manner 
      in vitro, accompanied by interferon-gamma release. In vivo, HA-1-specific CTLs 
      distribute systemically and prevent human breast cancer metastases in 
      immunodeficient mice. Moreover, HA-1-specific CTLs infiltrate and inhibit the 
      progression of fully established metastases. Our study provides the first proof 
      for the efficacy of a clinically applicable concept to exploit single mismatched 
      mHags with hematopoiesis- and solid tumor-restricted expression for boosting the 
      anti-solid tumor effect of allogeneic SCT.
FAU - Hambach, Lothar
AU  - Hambach L
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, The Netherlands. l.w.h.hambach@lumc.nl
FAU - Vermeij, Marcel
AU  - Vermeij M
FAU - Buser, Andreas
AU  - Buser A
FAU - Aghai, Zohara
AU  - Aghai Z
FAU - van der Kwast, Theodorus
AU  - van der Kwast T
FAU - Goulmy, Els
AU  - Goulmy E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080610
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (HA-1 antigen)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Oligopeptides)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Female
MH  - Graft vs Tumor Effect
MH  - Humans
MH  - Immunotherapy, Adoptive
MH  - Lung Neoplasms/immunology/pathology/prevention & control/secondary
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Minor Histocompatibility Antigens/*metabolism
MH  - Neoplasms/*immunology/pathology/*therapy
MH  - Oligopeptides/*metabolism
MH  - Stem Cell Transplantation
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Transplantation, Homologous
EDAT- 2008/06/12 09:00
MHDA- 2008/10/01 09:00
CRDT- 2008/06/12 09:00
PHST- 2008/06/12 09:00 [pubmed]
PHST- 2008/10/01 09:00 [medline]
PHST- 2008/06/12 09:00 [entrez]
AID - S0006-4971(20)49618-1 [pii]
AID - 10.1182/blood-2007-11-125492 [doi]
PST - ppublish
SO  - Blood. 2008 Sep 1;112(5):1844-52. doi: 10.1182/blood-2007-11-125492. Epub 2008 
      Jun 10.