5424066 Method for increasing CD4+ cell numbers through the use of monoclonal antibodies directed against self-reactive, CD4 specific cytotoxic T-cells

1996 ◽  
Vol 14 (3) ◽  
pp. 372
Blood ◽  
2009 ◽  
Vol 113 (11) ◽  
pp. 2442-2450 ◽  
Author(s):  
Chrystal U. Louis ◽  
Karin Straathof ◽  
Catherine M. Bollard ◽  
Claudia Gerken ◽  
M. Helen Huls ◽  
...  

Treatment of Epstein-Barr virus (EBV)–positive nasopharyngeal carcinoma (NPC) with EBV-specific cytotoxic T cells (EBV-specific CTL) has been promising, producing clinical responses. However, infused EBV-specific CTL did not expand in vivo, likely limiting their antitumor activity. Lymphodepleting patients with chemotherapy before T-cell transfer enhances in vivo T-cell expansion, but results in nonspecific destruction of the resident immune system and can have significant toxicity. To evaluate if monoclonal antibodies (mAbs) can produce a more selective lymphodepletion, we conducted a clinical study in which NPC patients received a pair of lymphodepleting mAbs targeted to the CD45 antigen (CD45 mAbs) before EBV-specific CTL infusion. Eight patients with recurrent NPC received CD45 mAbs followed by escalating doses of auto-logous EBV-specific CTL. Infusion of CD45 mAbs resulted in transient lymphopenia in all patients and an increase in interleukin-15 (IL-15) levels in 6 out 8 patients. All patients had an increase in their peripheral blood frequency of EBV-specific T cells after CTL infusion. Three patients with a persistent increase had clinical benefits including 1 complete response (> 24 months) and 2 with stable disease (for 12 and 15 months). Lymphodepleting mAbs prior CTL transfer may represent an alternative to chemotherapy to enhance expansion of infused CTL. This study is registered at http://www.clinialtrials.gov as NCT00608257.


1979 ◽  
Vol 150 (1) ◽  
pp. 166-163 ◽  
Author(s):  
R V Blanden ◽  
A Müllbacher ◽  
R B Ashman

Two different BALB/c anti-CBA (H-2k)monoclonal antibodies that bind to Kk and Dk antigens blocked Tc cell-mediated lysis of L929 (Kk, Dk) target cells, but with quite different specificity. One antibody (30R3) powerfully blocked Kk-specific lysis mediated by alloreactive or Kk-restricted Tc cells immune to ectromelia, Sendai, or influenza viruses. The other antibody (27R9) blocked these anti-Kk Tc cells much less than 30R3, but in contrast, 27R9 blocked anti-Dk lysis much more than 30R3. Most importantly, 27R9 strongly blocked Dk-restricted anti-influenza Tc cells, but did not significantly block Dk-restricted anti-Bebaru (BEB) lysis. This result indicated that different H-2 determinants coded in the D end of H-2k were recognized by influenza-and BEB-immune Tc cells. These determinants may be carried on two different molecules coded by the H-2D and H-2L loci, but other possibilities are not yet excluded.


1981 ◽  
Vol 154 (2) ◽  
pp. 563-568 ◽  
Author(s):  
M Brenan ◽  
A Mullbacher

Monoclonal antibodies directed to the D region of H-2(k) when present during in vitro culture inhibit the generation of CBA/H and C3H.H-2(o) H-Y-immune cytotoxic T cells . Monoclonal antibodies directed to the I-A(k) and I-E(k) region specifically inhibited induction of CBA/H H-Y-immune cytotoxic T cells only when they were present simultaneously in culture. These findings show T helper cell requirement for CBA/H H-Y-immune cytotoxic T cell induction, and suggest that two I region-coded restriction antigens for T helper cells are involved.


Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 752-757
Author(s):  
B Koziner ◽  
D Gebhard ◽  
T Denny ◽  
S McKenzie ◽  
BD Clarkson ◽  
...  

Leukemic cells in 134 patients with ALL were analyzed by a panel of mouse monoclonal antibodies. Two antibodies are reactive with all peripheral blood T cells but define different surface antigens (Leu-1 and Leu-4). Two other antibodies react with antigens that are restricted to suppressor/cytotoxic T cells (Leu-2) and to helper T cells (Leu-3). We also used antibodies to the receptor for sheep red blood cells (SRBC) (Leu-5) and to a human “TL-like” antigen that is found on most thymocytes but not in peripheral T cells (Leu-6). An antibody to the human p29.34 “Ia-like” molecule was also tested. Of the 134 ALL patients, 17 had a predominance of SRBC-rosetting (Leu-5+) lymphoblasts (“T” ALL), expressing different surface phenotypes defined by this panel of monoclonal antibodies. These phenotypes were not readily classifiable according to a scheme of sequential stages of normal differentiation proposed. Moreover, the lymphoblasts in 8 of 113 patients not expressing conventional B- to T-cell markers (“null” ALL) reacted with the monoclonal anti-T-cell antibodies. This study suggests that the classification of lymphoblasts in ALL based on the reactivities observed with this panel of mouse monoclonal antibodies is not easily reconciled with current models of normal T-cell differentiation. However, it should be emphasized that the precise sequence of antigenic expression by cells undergoing thymic differentiation is still not fully known, and further phenotypic analysis of ALL cells might contribute to an improved understanding of this malignancy.


2003 ◽  
Vol 71 (2) ◽  
pp. 956-963 ◽  
Author(s):  
Tammy A. Myers ◽  
Janet E. Leigh ◽  
Alfredo R. Arribas ◽  
Shannon Hager ◽  
Rebecca Clark ◽  
...  

ABSTRACT Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most frequent opportunistic fungal infection in human immunodeficiency virus (HIV)-positive persons. Although Th1-type CD4+ T cells are considered important for host defense against mucosal C. albicans infections, there is a paucity of information regarding the presence and/or role of T cells in OPC lesions. In pursuit of this, initial chromophore immunohistochemical studies showed a majority of CD8+ rather than CD4+ cells equally distributed throughout the buccal mucosa of OPC− persons (HIV− or HIV+), irrespective of blood CD4+ cell numbers. In contrast, CD8+ cells in lesions from HIV+ OPC+ persons were in significantly higher numbers and concentrated at the lamina propria-epithelium interface, a considerable distance from the Candida at the outer epithelium. Dual fluorescence and confocal microscopy confirmed that the majority of CD8+, but not CD4+, cells were T cells by the presence or absence, respectively, of CD3 on each cell type. These results suggest that CD8+ T cells may be important for oral host defense against OPC, especially when CD4 cell numbers are reduced, with a potential CD8 cell-specific dysfunction associated with susceptibility to OPC.


1988 ◽  
Vol 41 (4) ◽  
pp. 609-615 ◽  
Author(s):  
D. Mezzanzanica ◽  
S. Canevari ◽  
S. Ménard ◽  
S. M. Pupa ◽  
E. Tagliabue ◽  
...  

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