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Author Topic: anti-CD30 antibody exerts suppression on HIV replication  (Read 2086 times)

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Offline bimazek

  • Member
  • Posts: 781
anti-CD30 antibody exerts suppression on HIV replication
« on: January 23, 2007, 08:16:18 PM »
what do we do when a research company has a breakthru that could help hiv but they are focusing on cancer

could this antibody save people without so many side effects?

here is another anti-cd antibody with (after i researched it) anti-hiv properities possibly but medarex is not doing hiv trials.

MDX-1401 is anti-CD30 antibody

High serum level of the soluble form of CD30 molecule in the early phase of
HIV-1 infection as an independent predictor of progression to AIDS

Elevated serum levels of soluble (s)CD30 as well as following infection with human immuno-deficiency virus (HIV).

CD30 induces HIV expression in chronically infected T cells

independent prognostic indicator of disease progression, and the suggested role of CD30 in HIV-1 infection

Role for CD30 in HIV expression. ... Thus, CD30 triggering may play an important role
in both HIV replication and the death of HIV-infected CD4+ T cells

anti-CD30L antibody also exerted a suppressive effect on the spontaneous HIV replication occurring in lymph node cells, freshly derived from an HIV-seropositive patient showing CD30 expression in B cells and in a proportion of CD8+ T lymphocytes. Thus, CD30 triggering may play an important role in both HIV replication and the death of HIV-infected CD4+ T cells.



BioWa and Medarex Announce Allowance of Investigational New Drug Application for Second-Generation Anti-CD30 Antibody (MDX-1401) Enhanced Using Potelligent(TM) Technology

PRINCETON, N.J., Jan 09, 2007 BioWa, Inc. and Medarex, Inc. (Nasdaq: MEDX) announced today the allowance of an
investigational new drug application (IND) filed with the U.S. Food & Drug
Administration (FDA) for MDX-1401, a fully human antibody that targets CD30-positive
lymphomas. MDX-1401 is enhanced for greater Fc receptor mediated antibody activity,
one critical mechanism in tumor lysis by antibodies, using BioWa's Potelligent
Technology.

The dose-escalation, multi-dose Phase I clinical trial is expected to enroll up to
36 patients with relapsed or refractory Hodgkin's disease. The trial is designed to
establish and evaluate the safety profile and initial efficacy of MDX-1401.
Preclinical in vitro studies showed that this second- generation nonfucosylated
anti-CD30 antibody demonstrated enhanced antibody- dependent cellular cytotoxicity
(ADCC), an important mechanism of action of therapeutic antibodies, and was active
in inhibiting tumor growth in in vivo xenograft models.

"Today's announcement demonstrates our commitment to innovative approaches that have
the potential to enhance our fully human monoclonal antibody technology for
developing important new therapies," said Irwin Lerner, Chairman of the Board of
Directors and Interim President and CEO of Medarex. "We are pleased with our
partnership with BioWa and with its technology as a method for increasing the
potency of MDX-1401, a novel product that broadens our anti-CD30 clinical program
for Hodgkin's disease."
CD30, Th2 cytokines and HIV infection: a complex and fascinating link.Del Prete G, Maggi E, Pizzolo G, Romagnani S.
Division of Clinical Immunology and Allergy, University of Florence, Italy.




CD30 is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor superfamily, and was originally described as a marker of Hodgkin's and Reed-Sternberg cells in Hodgkin's lymphoma. CD30 is preferentially expressed on CD4+ and CD8+ T-cell clones that produce T helper 2 (Th2)-type cytokines, and is also released in a soluble form by these cells. Elevated serum levels of soluble (s)CD30 have been found in some conditions in which a pathogenic role for Th2 cells has been suggested, such as atopy, Omenn's syndrome, systemic lupus erythematosus, as well as following infection with measles virus or human immuno-deficiency virus (HIV). Here, Gianfranco Del Prete and colleagues suggest a complex and fascinating link between the expression and release of CD30, and the immunopathogenesis of HIV infection.



High serum level of the soluble form of CD30 molecule in the early phase of HIV-1 infection as an - group of 2
G Pizzolo, F Vinante, L Morosato, G Nadali, M - AIDS, 1994 - ncbi.nlm.nih.gov
High serum level of the soluble form of CD30 molecule in the early phase of
HIV-1 infection as an independent predictor of progression to AIDS. ...





Cross-linking of CD30 induces HIV expression in chronically infected T cells - group of 4
P Biswas, CA Smith, D Goletti, EC Hardy, RW - Immunity, 1995 - immunity.com
... Copyright 1995 . Immunity, Vol 2, 587-596, June 1995. Article. Cross-linking
of CD30 induces HIV expression in chronically infected T cells. .

 Vinante, A Rigo, MT Scupoli, G Pizzolo - Blood, 2002 - Am Soc Hematology
... at diagnosis have been shown to be an independent prognostic indicator of disease
progression, 22 , 23 and the suggested role of CD30 in HIV-1 infection 15 has ...

Regulation of CD30 Antigen Expression and Its Potential Significance for Human Disease - group of 2
ME Kadin - 2000 - ASIP
... 86. CD30 appears to be important in AIDS, where activation of CD30 enhances
HIV replication in CD4+ T cells from HIV-infected individuals. ...

Role for CD30 in HIV expression. - group of 2
S Romagnani, F Annunziato, R Manetti, F - Immunol Lett, 1996 - ncbi.nlm.nih.gov
Role for CD30 in HIV expression. ... Thus, CD30 triggering may play an important role
in both HIV replication and the death of HIV-infected CD4+ T cells. ...

Immune reconstitution inflammatory syndrome in HIV - group of 3
M Lipman, R Breen - Curr Opin Infect Dis, 2006 - co-infectiousdiseases.com
... of the effects of HAART demonstrated its potent and rapid suppression of HIV viraemia
and ... a Th2 bias, as shown by increased plasma levels of soluble CD30

CD4+ CD3-Cells Regulate the Organization of Lymphoid Tissue and T-Cell Memory for Antibody Responses - group of 3
PJL Lane, MY Kim, FMC Gaspal, FM McConnell - International Journal of Hematology, 2006 - Carden Jennings
... neonatal CD4 + CD3 inducer cells: evidence that IL-7 signals regulate CD30 ligand
but ... ten Velden J, Hack CE, Heeney JL.The relative resistance of HIV type 1 ..


 Volume 83, Number 1 / January 2006
     Pages:     12 - 16
     URL:     Linking Options

CD4+CD3- Cells Regulate the Organization of Lymphoid Tissue and T-Cell Memory for Antibody Responses

Peter J. L. Lane A1, Mi-Yeon Kim A1, Fabrina M. C. Gaspal A1, Fiona M. McConnell A1

A1 MRC Centre for Immune Regulation, Institute for Biomedical Research, Birmingham Medical School, Birmingham, UK

Abstract:

This review highlights the role of a CD4+CD3- accessory cell in the development of organized lymphoid infrastructures as well as in the development of high-affinity antibody responses and T-cell memory. These 2 functions are linked in the development of the vertebrate immune system and are effected by the constitutive expression of 2 sets of tumor necrosis factor (TNF) family members. The expression of lymphotoxin 3 (LT3), LT3, and TNF-3, which are closely linked genetically, affects the organization of lymphoid structures into B-cell and T-cell areas; the dual expression of OX40 ligand (TNFSF4) and CD30 ligand (TNFSF8) influences both the survival of T-cells within germinal centers and T-cell memory.


Role for CD30 in HIV expression.

    * Romagnani S,
    * Annunziato F,
    * Manetti R,
    * Almerigogna F,
    * Biagiotti R,
    * Giudizi MG,
    * Ravina A,
    * Gianno V,
    * Tomasevic L,
    * Maggi E.

Institute of Internal Medicine and Immunoallergology, University of Florence, Italy.

CD30 is a member of the tumor necrosis factor (TNF)-receptor superfamily, whose ligand (CD30L) has been identified on B cells, activated macrophages and a subset of activated T cells. We show here that infection in vitro with human immunodeficiency virus (HIV) of CD4+ T-cell clones generated from HIV-seronegative individuals can enhance the expression of CD30, which often preceeds and is associated with the death of clonal T cells. Furthermore, cross-linking CD30 with an agonistic CD30-specific monoclonal antibody potentiated HIV replication induced by an insolubilized anti-CD3 antibody in T-cell lines generated from HIV-infected individuals. More importantly, paraformaldehyde-fixed CD8+ T-cell clones expressing CD30L enhanced HIV replication in anti-CD3-stimulated allogeneic or autologous HIV-infected CD4+ T-cell lines and such a potentiating effect was inhibited by an anti-CD30L antibody. The anti-CD30L antibody also exerted a suppressive effect on the spontaneous HIV replication occurring in lymph node cells, freshly derived from an HIV-seropositive patient showing CD30 expression in B cells and in a proportion of CD8+ T lymphocytes. Thus, CD30 triggering may play an important role in both HIV replication and the death of HIV-infected CD4+ T cells.



This is a new antibody that as shown below has important effects in HIV disease, but this company is not doing any trials on HIV patients.

Do we need activism in New Jersey to ask for at least a dialogue.  Would activism and protests help the company get the publicity it needs to raise awareness so they can get the funding to do an HIV trial?  Can activists in NJ meet with them to discuss these issues.  Would having one hundred activists actively asking for this medicine improve thier ability to get funding?  Would the publicity raise the awareness in the investor community who are always willing to invest in something they see as potentially lucrative?

I believe the answer is yes.  Do we have activists in NJ?



 


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