Re: ASH: Bi20 a New Trifunctional Bispecific Antibody (CD20xCD3) for CLL

[Guest guest]

Thank you for sending these results, I have always believed that this

Bispecific AB could be our saviour, since it was first described. Keep up

the spirits and the good work

Dermot

ASH: Bi20 a New Trifunctional Bispecific Antibody

(CD20xCD3) for CLL

> [4910] Bi20 a New Trifunctional Bispecific Antibody (CD20xCD3) in the

> Treatment of Resistant B Cell Tumors: First Clinical Data. Session

> Type: Publication Only

>

> Belinda P. Simoes, Stanglmaier, Margot Faltin, Ruf,

> Christoph Schmid, a Bergmann, Maike Humann, Holger Wegner,

> Nicola Lang, Georg Ledderose, Horst Lindhofer, Hans-Jochem Kolb

> Medicine III, Ludwig Maximiliam University, Munich, Germany; Clinical

> ative Group SC Transplant, GSF Institute for Environment and

> Health, Munich, Germany; TRION Research, sried, Germany

>

> Here we describe the first clinical data of the new trifunctional

> bispecific antibody Bi20 (CD20xCD3). Bispecific antibodies that bind

> simultaneously to T cells (CD3) and to B-cells (CD20) have the

> potential to redirect T cells close to the tumor B cells and thereby

> increase cellular cytotoxicity. This trifunctional antibody not only

> binds to T cells and B cells, but also activates Fcg receptor I/III

> positive accessory cells.

> Three patients with advanced and refractory disease were treated: a

> 45 year old female with CLL, a 25 year old female with a diffuse

> large B-cell lymphoma (mediastinal mass) and a 29 year old man with a

> Burkitt-like lymphoma. Previous treatment of the three cases included

> various chemotherapy regimens, allogeneic bone marrow

> transplantation, donor lymphocyte infusions and monoclonal antibodies

> (Rituximab and Alemtuzumab). Patients received escalating doses of

> Bi20 thrice a week, starting with 10g up to 2000 g. Following the

> last antibody application donor T cells were infused. Reduction of

> peripheral B cells could already be seen with Bi20 doses as low as

> 80g and depletion was achieved with 600 g in the patient with CLL,

> demonstrating the high potency of this antibody. Moreover, in the

> first patient who presented with a p53 deletion population in bone

> marrow, these highly resistant cells were completely eliminated as

> shown by FISH analysis. In the second case, disease progression was

> halted (PET analysis), actually for more than four months. In the

> third patient, with a very high tumor mass, reduction in tumor growth

> was only transient with no further benefit.

> The antibody was well tolerated in all cases, with fever and chills

> as the major complications. The secretion of cytokines (IL2, IL4,

> IL6, IL8, IL10, IL12, TNFa, IFNg and GM-CSF) was followed during the

> treatment and the inflammatory reactions correlated with the release

> of cytokines, especially IL-6, and IFNg. Prolonging the infusion time

> easily controlled the side effects. Although the second and third

> patient received T cell transfusions from their HLA-haploidentical

> stem cell donor no GVHD was observed.

> These preliminary clinical data demonstrate the safety and potency of

> this new trifunctional antibody, seen not only in the ability to

> clear tumor B cells from peripheral blood at very low concentrations,

> but also to eliminate otherwise highly resistant tumor cells in the

> bone marrow. The absence of GVHD following Bi20 and T cell

> transfusions suggests that T cell responses are redirected against

> the tumor cells (GVL) without producing GVHD.

> BPS was supported by grant nr. 01/04492-8 from FAPESP (Fundacao de

> Amparo a Pesquisa do Estado de Sao o Brazil).

> Abstract #4910 appears in Blood, Volume 102, issue 11, November 16,

> 2003

> Keywords: Bispecific Antibody|Cellular Immunity|Stem Cell

> Transplantation

>

> Publication Only

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