Abstract |
In contrast to other neoplasms, antigen-specific autologous cytolytic T cells have not been detected in patients with human pre-B-cell leukemias. The absence of efficient B7 family (B7-1/CD80; B7-2/CD86) -mediated costimulation has been shown to be a major defect in tumor cells' capacity to function as antigen-presenting cells. We show here the generation of autologous anti- pre-B-cell leukemia-specific cytolytic T-cell lines from the marrows of 10 of 15 patients with pre-B-cell malignancies. T-cell costimulation via CD28 is an absolute requirement for the generation of these autologous cytolytic T cells (CTL). Although costimulation could be delivered by either bystander B7 transfectants or professional antigen-presenting cells (indirect costimulation), optimal priming and CTL expansion required that the costimulatory signal was expressed by the tumor cell (direct costimulation). These anti- pre-B-cell leukemia-specific CTL lysed both unstimulated and CD40-stimulated tumor cells from each patient studied but did not lyse either K562 or CD40-stimulated allogeneic B cells. Cytolysis was mediated by the induction of tumor cell apoptosis by CD8+ T cells via the perforin- granzyme pathway. Although we were able to generate anti- leukemia-specific CTL from the bone marrow, we were unable to generate such CTL from the peripheral blood of these patients. These studies show that antigen-specific CTL can be generated from the bone marrow of patients with pre-B-cell leukemias and these findings should facilitate the design of adoptive T-cell-mediated immunotherapy trials for the treatment of patients with B-cell precursor malignancies.
|
Authors | A A Cardoso, M J Seamon, H M Afonso, P Ghia, V A Boussiotis, G J Freeman, J G Gribben, S E Sallan, L M Nadler |
Journal | Blood
(Blood)
Vol. 90
Issue 2
Pg. 549-61
(Jul 15 1997)
ISSN: 0006-4971 [Print] United States |
PMID | 9226154
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Antigens, CD
- B7-1 Antigen
- B7-2 Antigen
- CD86 protein, human
- Membrane Glycoproteins
- Recombinant Fusion Proteins
- Interferon-gamma
|
Topics |
- Animals
- Antigens, CD
(biosynthesis, immunology)
- Apoptosis
- B7-1 Antigen
(biosynthesis, immunology)
- B7-2 Antigen
- Bone Marrow
(immunology, pathology)
- Burkitt Lymphoma
(immunology, pathology)
- CHO Cells
- Cells, Cultured
- Cricetinae
- DNA Fragmentation
- Dendritic Cells
(immunology)
- Humans
- Immunophenotyping
- Interferon-gamma
(biosynthesis)
- Leukemia, B-Cell
(immunology, pathology)
- Lymphocyte Culture Test, Mixed
- Membrane Glycoproteins
(biosynthesis, immunology)
- Preleukemia
(immunology, pathology)
- Recombinant Fusion Proteins
(biosynthesis)
- Reference Values
- T-Lymphocytes
(immunology)
- T-Lymphocytes, Cytotoxic
(immunology, pathology)
- Tumor Cells, Cultured
|