scholarly journals Increased lysis of patient CD10-positive leukemic cells by T cells coated with anti-CD3 Fab' antibody cross-linked to anti-CD10 Fab' antibody

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1044-1049 ◽  
Author(s):  
K Oshimi ◽  
T Seto ◽  
Y Oshimi ◽  
M Masuda ◽  
K Okumura ◽  
...  

Abstract An anti-CD3 Fab' x anti-CD10 Fab' bispecific hybrid F(ab')2 antibody (Ab) was generated. This bispecific Ab had a molecular mass of 100 to 110 Kd, and the capacity to react with both CD3+ T cells and CD10+ acute lymphoblastic leukemia (ALL) cells. We studied whether cytotoxic T lymphocytes (CTLs) could lyse patient CD10+ ALL cells after addition of the bispecific Ab. As effector CTLs, interleukin-2 (IL-2)-stimulated peripheral blood mononuclear cells (PBMCs) and CTL clones were used. When IL-2-stimulated PBMCs were assayed for cytotoxicity to 61Cr- labeled CD10+ ALL cells, their activity was shown to be markedly enhanced by the addition of the bispecific Ab. Most of the CTL clones established lacked cytotoxicity for CD10+ ALL cells, but addition of the bispecific Ab induced a significant level of cytotoxicity. CTLs derived from ALL patients also showed significant cytotoxicity for autologous CD10+ ALL cells after addition of the bispecific Ab. However, this Ab did not affect the cytotoxicity of CTLs when CD10- leukemic cells were used as the targets. These findings suggest that the bispecific Ab can be used for immunotherapy in patients with CD10+ ALL.

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1044-1049
Author(s):  
K Oshimi ◽  
T Seto ◽  
Y Oshimi ◽  
M Masuda ◽  
K Okumura ◽  
...  

An anti-CD3 Fab' x anti-CD10 Fab' bispecific hybrid F(ab')2 antibody (Ab) was generated. This bispecific Ab had a molecular mass of 100 to 110 Kd, and the capacity to react with both CD3+ T cells and CD10+ acute lymphoblastic leukemia (ALL) cells. We studied whether cytotoxic T lymphocytes (CTLs) could lyse patient CD10+ ALL cells after addition of the bispecific Ab. As effector CTLs, interleukin-2 (IL-2)-stimulated peripheral blood mononuclear cells (PBMCs) and CTL clones were used. When IL-2-stimulated PBMCs were assayed for cytotoxicity to 61Cr- labeled CD10+ ALL cells, their activity was shown to be markedly enhanced by the addition of the bispecific Ab. Most of the CTL clones established lacked cytotoxicity for CD10+ ALL cells, but addition of the bispecific Ab induced a significant level of cytotoxicity. CTLs derived from ALL patients also showed significant cytotoxicity for autologous CD10+ ALL cells after addition of the bispecific Ab. However, this Ab did not affect the cytotoxicity of CTLs when CD10- leukemic cells were used as the targets. These findings suggest that the bispecific Ab can be used for immunotherapy in patients with CD10+ ALL.


Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1595-1603 ◽  
Author(s):  
K Welte ◽  
CA Keever ◽  
J Levick ◽  
MA Bonilla ◽  
VJ Merluzzi ◽  
...  

Abstract The ability of peripheral blood mononuclear cells (PBMC) to produce and respond to interleukin-2 (IL-2) was evaluated in 50 recipients of HLA- identical bone marrow (BM) depleted of mature T cells by soybean agglutination and E rosetting (SBA-E-BM). In contrast to our previous findings in recipients of unfractionated marrow, during weeks 3 to 7 post-SBA-E-BM transplantation (BMT), PBMC from the majority of patients spontaneously released IL-2 into the culture medium. This IL-2 was not produced by Leu-11+ natural killer cells, which were found to be predominant in the circulation at this time, but by T11+, T3+, Ia antigen-bearing T cells. The IL-2 production could be enhanced by coculture with host PBMC frozen before transplant but not by stimulation with mitogenic amounts of OKT3 antibody, thus suggesting an in vivo activation of donor T cells or their precursors by host tissue. Spontaneous IL-2 production was inversely proportional to the number of circulating peripheral blood lymphocytes and ceased after 7 to 8 weeks post-SBA-E-BMT in most of the patients. In patients whose cells had ceased to produce IL-2 spontaneously or never produced this cytokine, neither coculture with host cells nor stimulation with OKT3 antibody thereafter induced IL-2 release through the first year posttransplant. Proliferative responses to exogenous IL-2 after stimulation with OKT3 antibody remained abnormal for up to 6 months post-SBA-E-BMT, unlike the responses of PBMC from recipients of conventional BM, which responded normally by 1 month post-BMT. However, the upregulation of IL- 2 receptor expression by exogenous IL-2 was found to be comparable to normal controls when tested as early as 3 weeks post-SBA-E-BMT. Therefore, the immunologic recovery of proliferative responses to IL-2 and the appearance of cells regulating in vivo activation of T cells appear to be more delayed in patients receiving T cell-depleted BMT. Similar to patients receiving conventional BMT, however, the ability to produce IL-2 after mitogenic stimulation remains depressed for up to 1 year after transplantation.


2016 ◽  
Vol 49 (2) ◽  
pp. 675-681 ◽  
Author(s):  
María Sánchez-Cuaxospa ◽  
Alejandra Contreras-Ramos ◽  
Erandi Pérez-Figueroa ◽  
Aurora Medina-Sansón ◽  
Elva Jiménez-Hernández ◽  
...  

2021 ◽  
Vol 17 (3) ◽  
pp. 460-470
Author(s):  
Mohd Wajid Ali Khan ◽  

Human Vγ9/Vδ2 T cells (γδ T cells) are immune surveillance cells both in innate and adaptive immunity and are a possible target for anticancer therapies, which can induce immune responses in a variety of cancers. Small non-peptide antigens such as zoledronate can do activation and expansion of T cells in vitro. It is evident that for adoptive cancer therapies, large numbers of functional cells are needed into cancer patients. Hence, optimization of methods needs to be carried out for the efficient expansion of these T cells. Standardization of peripheral blood mononuclear cells (PBMCs) isolation was devised. Cytokines (interleukin 2 (IL-2) and interleukin 15 (IL-15)) and zoledronate were also standardized for different concentrations. It was found that an increased number of PBMCs were recovered when washing was done at 1100 revolution per minute (rpm). Significantly high expansion fold was (2524 ± 787 expansion fold) achieved when stimulation of PBMCs was done with 1 μM of zoledronate and both cytokines IL-2 and IL-15 supported the expansion and survival of cells ISSN 0973-2063 (online) 0973-8894 (print) Bioinformation 17(3): 460-469 (2021) ©Biomedical Informatics (2021) 461 at the concentrations of 100 IU/ml and 10 ng/ml respectively. 14-day cultures showed highly pure (91.6 ± 5.1%) and live (96.5 ± 2.5%) expanded γδ T cells. This study aimed to standardize an easy to manipulate technique for the expansion of γδ T cells, giving a higher yield.


Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1595-1603 ◽  
Author(s):  
K Welte ◽  
CA Keever ◽  
J Levick ◽  
MA Bonilla ◽  
VJ Merluzzi ◽  
...  

The ability of peripheral blood mononuclear cells (PBMC) to produce and respond to interleukin-2 (IL-2) was evaluated in 50 recipients of HLA- identical bone marrow (BM) depleted of mature T cells by soybean agglutination and E rosetting (SBA-E-BM). In contrast to our previous findings in recipients of unfractionated marrow, during weeks 3 to 7 post-SBA-E-BM transplantation (BMT), PBMC from the majority of patients spontaneously released IL-2 into the culture medium. This IL-2 was not produced by Leu-11+ natural killer cells, which were found to be predominant in the circulation at this time, but by T11+, T3+, Ia antigen-bearing T cells. The IL-2 production could be enhanced by coculture with host PBMC frozen before transplant but not by stimulation with mitogenic amounts of OKT3 antibody, thus suggesting an in vivo activation of donor T cells or their precursors by host tissue. Spontaneous IL-2 production was inversely proportional to the number of circulating peripheral blood lymphocytes and ceased after 7 to 8 weeks post-SBA-E-BMT in most of the patients. In patients whose cells had ceased to produce IL-2 spontaneously or never produced this cytokine, neither coculture with host cells nor stimulation with OKT3 antibody thereafter induced IL-2 release through the first year posttransplant. Proliferative responses to exogenous IL-2 after stimulation with OKT3 antibody remained abnormal for up to 6 months post-SBA-E-BMT, unlike the responses of PBMC from recipients of conventional BM, which responded normally by 1 month post-BMT. However, the upregulation of IL- 2 receptor expression by exogenous IL-2 was found to be comparable to normal controls when tested as early as 3 weeks post-SBA-E-BMT. Therefore, the immunologic recovery of proliferative responses to IL-2 and the appearance of cells regulating in vivo activation of T cells appear to be more delayed in patients receiving T cell-depleted BMT. Similar to patients receiving conventional BMT, however, the ability to produce IL-2 after mitogenic stimulation remains depressed for up to 1 year after transplantation.


Blood ◽  
1980 ◽  
Vol 56 (3) ◽  
pp. 380-382
Author(s):  
J Blatt ◽  
GH Reaman ◽  
N Levin ◽  
DG Poplack

Purine nucleoside phosphorylase (PNP) activity has been measured in the lymphoblasts of 22 patients with acute lymphoblastic leukemia (ALL) and correlated with routine immunologic cell surface markers. Fourteen of the 22 patients were considered to have non-T, non-B-cell ALL; 8 patients had T-cell disease. The median PNP activity in 21 control samples of normal peripheral blood mononuclear cells was 83 U. The median PNP activity of the non-T, non-B lymphoblasts was 79 U. No statistical difference in PNP activity between these two groups could be discerned (p < 0.37). In contrast, T-cell lymphoblasts demonstrated diminished PNP activity with a median of 38 U. The differences in activity between T lymphoblasts and both non-T, non-B leukemic cells and normal peripheral blood mononuclear cells were significant (p < 0.001 and p < 0.003, respectively). Evaluation of PNP activity provides further evidence of biochemical heterogeneity among immunologic subclasses of ALL.


Blood ◽  
1980 ◽  
Vol 56 (3) ◽  
pp. 380-382 ◽  
Author(s):  
J Blatt ◽  
GH Reaman ◽  
N Levin ◽  
DG Poplack

Abstract Purine nucleoside phosphorylase (PNP) activity has been measured in the lymphoblasts of 22 patients with acute lymphoblastic leukemia (ALL) and correlated with routine immunologic cell surface markers. Fourteen of the 22 patients were considered to have non-T, non-B-cell ALL; 8 patients had T-cell disease. The median PNP activity in 21 control samples of normal peripheral blood mononuclear cells was 83 U. The median PNP activity of the non-T, non-B lymphoblasts was 79 U. No statistical difference in PNP activity between these two groups could be discerned (p < 0.37). In contrast, T-cell lymphoblasts demonstrated diminished PNP activity with a median of 38 U. The differences in activity between T lymphoblasts and both non-T, non-B leukemic cells and normal peripheral blood mononuclear cells were significant (p < 0.001 and p < 0.003, respectively). Evaluation of PNP activity provides further evidence of biochemical heterogeneity among immunologic subclasses of ALL.


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