Limits...
T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor.

Lee YS, Kim TS, Kim DK - BMC Cancer (2011)

Bottom Line: Although the graft-versus-tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB) transplantation have not been well studied.NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death.In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays.

View Article: PubMed Central - HTML - PubMed

Affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Graduate School of Life Science and Biotechnology, CHA University, Seoul, Republic of Korea.

ABSTRACT

Background: Although the graft-versus-tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB) transplantation have not been well studied.

Methods: We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells.

Results: We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays.

Conclusions: Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.

Show MeSH

Related in: MedlinePlus

Antitumor activity of T lymphocytes to cervical and lung tumors in NOD/SCID mice with and without previously injected cord blood. A, representative tumors size and weight at 8 weeks after injection with A549 (2 × 106 cells) into mice with or without previous cord blood transfer were shown (* P <0.05). B and C, The size and weight of tumors were measured 8 weeks after subcutaneous injection of Caski (B) or HeLa (C) cervical cancer cells without and with CB T-cell grafts (* P <0.05). D, phenotype of cells from splenocytes of mice with T-cell grafts followed by injections with Caski cells; flow cytometry analysis with antibodies to CD3, CD45RO, and CD45RA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3141763&req=5

Figure 3: Antitumor activity of T lymphocytes to cervical and lung tumors in NOD/SCID mice with and without previously injected cord blood. A, representative tumors size and weight at 8 weeks after injection with A549 (2 × 106 cells) into mice with or without previous cord blood transfer were shown (* P <0.05). B and C, The size and weight of tumors were measured 8 weeks after subcutaneous injection of Caski (B) or HeLa (C) cervical cancer cells without and with CB T-cell grafts (* P <0.05). D, phenotype of cells from splenocytes of mice with T-cell grafts followed by injections with Caski cells; flow cytometry analysis with antibodies to CD3, CD45RO, and CD45RA.

Mentions: To assess antitumor activity of CB-T cells in vivo, 2 × 106 cervical tumor cells (Caski or HeLa) or lung tumor cells (A549) were subcutaneously injected in the right flank of mice that either had or had not been previously injected with CB-T cells. Eight weeks after the tumor-cell injection, the mice were sacrificed and the volume and weight of the tumor were determined. The CB-T cells pre-reconstituted NOD/SCID mice before tumor injection showed significant inhibition of tumor growth in both cervical and lung cancer injected mice, while the control mice without CB-T cells did not show inhibition of tumor growth (Figure 3A, B and 3C). Phenotypic analysis of antitumor CD3+ T cells from spleen, peripheral blood and tumors showed a majority of CD45RO+ T cells, but few CD45RA+ T cells (Figure 3D). On immunohistochemical analysis, we observed high numbers of CD8+ T cells and CD4+ T cells near one another in the tumors formed by Caski and HeLa cervical cancer cells, as well as A549 lung cancer (Figure 4A). In addition, CD8+ T cells were present in high concentrations in both tumor tissues while CD4+ T cells were at a much higher concentration in Caski-cell tumors than in HeLa-cell tumors. From flow cytometry analysis, we confirmed that a relatively high proportion of the CD3+ T cells were present in the hematopoietic organs of mice that had Caski-cell injections. The TUNEL assay, a test for apoptotic cells, was highly positive in Caski and HeLa tumor tissue (Figure 4B). These results suggest that CB-T cells induced tumor apoptosis directly, resulting in dramatic tumor remission.


T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor.

Lee YS, Kim TS, Kim DK - BMC Cancer (2011)

Antitumor activity of T lymphocytes to cervical and lung tumors in NOD/SCID mice with and without previously injected cord blood. A, representative tumors size and weight at 8 weeks after injection with A549 (2 × 106 cells) into mice with or without previous cord blood transfer were shown (* P <0.05). B and C, The size and weight of tumors were measured 8 weeks after subcutaneous injection of Caski (B) or HeLa (C) cervical cancer cells without and with CB T-cell grafts (* P <0.05). D, phenotype of cells from splenocytes of mice with T-cell grafts followed by injections with Caski cells; flow cytometry analysis with antibodies to CD3, CD45RO, and CD45RA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3141763&req=5

Figure 3: Antitumor activity of T lymphocytes to cervical and lung tumors in NOD/SCID mice with and without previously injected cord blood. A, representative tumors size and weight at 8 weeks after injection with A549 (2 × 106 cells) into mice with or without previous cord blood transfer were shown (* P <0.05). B and C, The size and weight of tumors were measured 8 weeks after subcutaneous injection of Caski (B) or HeLa (C) cervical cancer cells without and with CB T-cell grafts (* P <0.05). D, phenotype of cells from splenocytes of mice with T-cell grafts followed by injections with Caski cells; flow cytometry analysis with antibodies to CD3, CD45RO, and CD45RA.
Mentions: To assess antitumor activity of CB-T cells in vivo, 2 × 106 cervical tumor cells (Caski or HeLa) or lung tumor cells (A549) were subcutaneously injected in the right flank of mice that either had or had not been previously injected with CB-T cells. Eight weeks after the tumor-cell injection, the mice were sacrificed and the volume and weight of the tumor were determined. The CB-T cells pre-reconstituted NOD/SCID mice before tumor injection showed significant inhibition of tumor growth in both cervical and lung cancer injected mice, while the control mice without CB-T cells did not show inhibition of tumor growth (Figure 3A, B and 3C). Phenotypic analysis of antitumor CD3+ T cells from spleen, peripheral blood and tumors showed a majority of CD45RO+ T cells, but few CD45RA+ T cells (Figure 3D). On immunohistochemical analysis, we observed high numbers of CD8+ T cells and CD4+ T cells near one another in the tumors formed by Caski and HeLa cervical cancer cells, as well as A549 lung cancer (Figure 4A). In addition, CD8+ T cells were present in high concentrations in both tumor tissues while CD4+ T cells were at a much higher concentration in Caski-cell tumors than in HeLa-cell tumors. From flow cytometry analysis, we confirmed that a relatively high proportion of the CD3+ T cells were present in the hematopoietic organs of mice that had Caski-cell injections. The TUNEL assay, a test for apoptotic cells, was highly positive in Caski and HeLa tumor tissue (Figure 4B). These results suggest that CB-T cells induced tumor apoptosis directly, resulting in dramatic tumor remission.

Bottom Line: Although the graft-versus-tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB) transplantation have not been well studied.NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death.In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays.

View Article: PubMed Central - HTML - PubMed

Affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Graduate School of Life Science and Biotechnology, CHA University, Seoul, Republic of Korea.

ABSTRACT

Background: Although the graft-versus-tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB) transplantation have not been well studied.

Methods: We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells.

Results: We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays.

Conclusions: Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.

Show MeSH
Related in: MedlinePlus