scholarly journals Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer

Blood ◽  
1996 ◽  
Vol 88 (4) ◽  
pp. 1501-1508 ◽  
Author(s):  
B Eibl ◽  
H Schwaighofer ◽  
D Nachbaur ◽  
C Marth ◽  
A Gachter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
T Lymphocytes ◽  
Solid Tumors ◽  
Cytotoxic T Lymphocytes ◽  
Antitumor Effect ◽  
Allogeneic Bone Marrow Transplantation ◽  
Breast Cancer Cell Lines ◽  
Target Cells ◽  
Allogeneic Bone

Graft-versus-leukemia (GvL) has been shown to be an important immune- mediated antitumor effect in hematologic malignancies. It is still unknown whether such an immunemediated antitumor effect has clinical implications in patients with solid tumors. A 32-year-old woman with inflammatory breast cancer received a bone marrow transplant (BMT) from her HLA-identical sibling. During graft-versus-host disease (GvHD) cytotoxic T lymphocytes were grown and tested in a chromium-release assay against B and T lymphocytes of the patient and donor and against a panel of breast cancer cell lines. Resolution of liver metastases was observed simultaneously with clinical GvHD in the first weeks after transplant. In addition, minor histocompatibility antigen (MiHA)- specific and major histocompatibility complex (MHC) class I antigen- restricted cytotoxic T lymphocytes recognizing breast carcinoma target cells were isolated from the blood of the patient. Pretreatment of such target cells with tumor necrosis factor (TNF)-alpha but not with interferon (IFN)-alpha or IFN-gamma increased susceptibility of these cells to lysis by cytotoxic T lymphocytes. Clinical course and in vitro results suggest that a graft-versus-tumor (GvT) effect might exist after allogeneic BMT for breast cancer. However, clinical experience on a larger scale would be required to determine the clinical efficacy of GvT effects in patients with solid tumors.

scholarly journals A large proportion of T lymphocytes lack CD5 expression after bone marrow transplantation

Blood ◽  
1989 ◽  
Vol 73 (5) ◽  
pp. 1359-1366
Author(s):  
BE Bierer ◽  
SJ Burakoff ◽  
BR Smith
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Lymphocytes ◽  
Marrow Transplantation ◽  
Normal Population ◽  
Allogeneic Bone Marrow Transplantation ◽  
Interleukin 2 ◽  
Significant Proportion ◽  
Allogeneic Bone

The lymphocyte cell surface molecule CD5 (T1, Leu 1, Tp67 in the human; Ly 1 in the mouse) is expressed on the majority of circulating T lymphocytes and a small population of B cells. We have analyzed CD5 expression on repopulating T cells in the peripheral blood of patients after allogeneic bone marrow transplantation (BMT). The frequency of CD3+ T cells that lack expression of CD5 is dramatically increased after BMT compared with the normal population. The percent of total CD3+ CD5- cells correlated with the presence of graft versus host disease and with time following transplant, but did not correlate with age, diagnosis, preparative regimen, T-cell depletion of the marrow, major histocompatibility complex compatibility, or the presence or absence of interstitial pneumonitis. Furthermore, the total number and percent of CD8+ CD5- cells was increased following BMT. CD3+ cells from BMT patients were sorted for the presence or absence of CD5 expression. CD3+ CD5- cells were capable of interleukin-2 production and of mediating cytolysis following lectin stimulation. We conclude that CD3+ CD5- T cells are functional and represent a significant proportion of circulating cells in patients after BMT.

scholarly journals Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigen in vivo.

1996 ◽  
Vol 183 (1) ◽  
pp. 317-322 ◽  
Author(s):  
P Paglia ◽  
C Chiodoni ◽  
M Rodolfo ◽  
M P Colombo
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Soluble Protein ◽  
Target Cells ◽  
Gm Csf ◽  
Dc Line

The priming of an immune response against a major histocompatibility complex class I-restricted antigen expressed by nonhematopoietic cells involves the transfer of that antigen to a host bone marrow-derived antigen presenting cell (APC) for presentation to CD8+ T lymphocytes. Dendritic cells (DC), as bone marrow-derived APC, are first candidates for presentation of tumor-associated antigens (TAA). The aim of this study was to see whether DC are able to prime in vivo antigen-specific cytotoxic T lymphocytes after exposure to a soluble protein antigen in vitro. Lacking a well-defined murine TAA, we took advantage of beta-galactosidase (beta-gal)-transduced tumor cell lines as a model in which beta-gal operationally functions as TAA. For in vivo priming both a DC line, transduced or not transduced with the gene coding for murine GM-CSF, and fresh bone marrow-derived DC (bm-DC), loaded in vitro with soluble beta-gal, were used. Priming with either granulocyte macrophage colony-stimulating factor-transduced DC line or fresh bm-DC but not with untransduced DC line generated CTL able to lyse beta-gal-transfected target cells. Furthermore, GM-CSF was necessary for the DC line to efficiently present soluble beta-gal as an H-2Ld-restricted peptide to a beta-gal-specific CTL clone. Data also show that a long-lasting immunity against tumor challenge can be induced using beta-gal-pulsed bm-DC as vaccine. These results indicate that effector cells can be recruited and activated in vivo by antigen-pulsed DC, providing an efficient immune reaction against tumors.

Rapid expansion of cytomegalovirus–specific cytotoxic T lymphocytes by artificial antigen-presenting cells expressing a single HLA allele

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2498-2505 ◽  
Author(s):  
Genovefa A. Papanicolaou ◽  
Jean-Baptiste Latouche ◽  
Cuiwen Tan ◽  
Jakob Dupont ◽  
Jeffrey Stiles ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood ◽  
Allogeneic Bone Marrow Transplantation ◽  
Antigen Presenting Cells ◽  
Full Length ◽  
Rapid Expansion ◽  
Allogeneic Bone ◽  
Specific Ctls ◽  
Antigen Presenting

Abstract Cytomegalovirus (CMV) is a major threat in patients undergoing allogeneic bone marrow transplantation. The adoptive transfer of CMV-specific cytotoxic T lymphocytes (CTLs) expanded from the blood of CMV-seropositive donors has been shown to effectively control CMV infection. However, the requirement for safe and effective antigen-presenting cells (APCs) for each patient precludes broad applicability of this successful form of therapy. Here we analyze the ability of artificial APCs (AAPCs) to activate and expand CMV-specific CTLs from peripheral blood of seropositive HLA A2.1+ donors. We demonstrate that AAPCs expressing the CMV P495 peptide or the full-length pp65 protein stimulate P495-specific CTLs at least as effectively as autologous, peptide-pulsed, peripheral blood mononuclear cells or EBV-transformed B cells. Starting from 100 mL of blood, the AAPCs reliably yield clinically relevant CTL numbers after a single stimulation. CTLs activated on AAPCs effectively kill CMV-infected fibroblasts and have a Tc1 memory effector phenotype identical to that of CTLs generated with autologous APCs. AAPCs thus offer a rapid, controlled, convenient, and highly reproducible system for expanding CMV-specific CTLs. Furthermore, the CTL expansion obtained with AAPCs encoding full-length pp65 indicates that AAPCs may be used to present known as well as unknown CTL epitopes in the context of the AAPC's HLA. (Blood. 2003;102:2498-2505)

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