scholarly journals Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor

1981 ◽  
Vol 154 (5) ◽  
pp. 1403-1418 ◽  
Author(s):  
JE Gootenberg ◽  
FW Ruscetti ◽  
JW Mier ◽  
A Gazdar ◽  
RC Gallo

Three cell lines of mature T cell origin derived from patients with cutaneous T cell lymphoma-leukemias (CTCL) were found to be constitutive producers of T cell growth factor (L-TCGF). These are the first reported human cell lines which constitutively produce TCGF. Biologically active TCGF could also be eluted from the surface of these cells using an acid glycine buffer under conditions that maintained cell viability, and subcellular fractionation showed that almost all the TCGF activity was associated with the plasma membrane. Over 30 other human hematopoietic cell lines derived from other disorders were unable to produce TCGF even after induction, and their acid eluates did not contain TCGF activity. L-TCGF from CTCL lines had the same biological activity as TCGF obtained from normal leukocytes (N-TCGF) in that they both supported the long-term growth of normal T cells only after the cells were previously activated by antigen or lectin. Both L-TCGF and N-TCGF increased the rate of proliferation of TCGF-independent and TCGF-dependent CTCL cell lines. The same three factor-independent cell lines that released TCGF adsorbed TCGF in a cell-concentration, time-, and temperature-dependent manner. Since the CTCL cell lines produce TCGF, adsorb TCGF, and increase their proliferative rate in response to TCGF or a related molecule, it is suggested that this endogenously produced factor plays a role in maintaining the abnormal proliferation of these cells in culture as permanently growing cell lines independent of exogenous TCGF. However, this does not mean that this is an essential aspect of neoplastic transformation. Since it is unusual to develop these cell lines in the absence of the continuous need for added TCGF, "autostimulation" may be one of the many unusual variant phenotypic properties sometimes associated with neoplastic cells that gives them a selective advantage for in vitro growth.

1998 ◽  
Vol 155 (2) ◽  
pp. 170-177 ◽  
Author(s):  
Jun-ichi Satoh ◽  
Kazuhiro Kurohara ◽  
Motohiro Yukitake ◽  
Yasuo Kuroda

Blood ◽  
1982 ◽  
Vol 59 (6) ◽  
pp. 1330-1336 ◽  
Author(s):  
C Tarella ◽  
FW Ruscetti ◽  
BJ Poiesz ◽  
A Woods ◽  
RC Gallo

Abstract Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis.


1980 ◽  
Vol 77 (11) ◽  
pp. 6815-6819 ◽  
Author(s):  
B. J. Poiesz ◽  
F. W. Ruscetti ◽  
J. W. Mier ◽  
A. M. Woods ◽  
R. C. Gallo

1981 ◽  
Vol 43 (2) ◽  
pp. 99-103 ◽  
Author(s):  
Roland Mertelsmann ◽  
Steven Gillis ◽  
Gerd Steinmann ◽  
Peter Ralph ◽  
Matthias Stiehm ◽  
...  

1980 ◽  
Vol 1 (3) ◽  
pp. 254
Author(s):  
Devendra Dubey ◽  
Stephen Stux ◽  
Y. Kai Tsong ◽  
Edmond J. Yunis

Blood ◽  
1982 ◽  
Vol 59 (6) ◽  
pp. 1330-1336
Author(s):  
C Tarella ◽  
FW Ruscetti ◽  
BJ Poiesz ◽  
A Woods ◽  
RC Gallo

Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis.


Author(s):  
Chi-Heng Wu ◽  
Linlin Wang ◽  
Chen-Yen Yang ◽  
Kwun Wah Wen ◽  
Brian R Hinds ◽  
...  

CD70 is a member of the tumor necrosis factor (TNF) receptor superfamily. Emerging data indicate that CD70 may be a suitable target for various malignancies. We investigated the expression of CD70 in cutaneous and systemic T cell lymphomas; and conducted pre-clinical studies of SGN-CD70A, a CD70-directed antibody-drug conjugate, using patient-derived cutaneous T cell lymphoma (CTCL PDX) models. CD70 expression was examined by immunohistochemical stains in 46 diagnostic specimens of T cell lymphomas. The activities of SGN-CD70A in growth inhibition and apoptosis induction were examined in CTCL cell lines and primary CTCL tumor cells. Using previously established CTCL PDXs, we conducted a dose-finding trial, followed by a phase II-like trial, to evaluate the optimal dosing and the efficacy of SGN-CD70A in tumor-bearing PDX animals. The therapeutic efficacy of SGN-CD70A was measured by tumor-associated cell-free DNA (cfDNA) and survival of treated PDXs. We found that CD70 is highly expressed in T cell lymphomas, especially in CTCL. SGN-CD70A inhibited cell growth and induced apoptosis in CD70-expressing CTCL cell-lines and primary tumors cells. Additionally, SGN-CD70A at 100 µg/kg and 300 µg/kg prolonged survival of PDXs in a dose-dependent manner. Finally, treatment with three doses of SGN-CD70A at 300 µg/kg was superior to single dose treatment in survival prolongation (median survival: 111 days vs. 39 days, p=0.017). Most importantly, multiple-dosing of SGN-CD70A induced complete eradication of established tumors in PDXs measured by cfDNA. Our results demonstrated marked anti-tumor activity of SGN-CD70A in CTCL PDXs, providing compelling support for its clinical investigation.


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