Bispecific antibodies that bind CD 123 CD3
A bispecific, antibody technology, applied in the direction of antibodies, antibody medical components, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
example
[0365] The following examples are provided to illustrate the invention. These examples are not intended to limit the invention to any particular application or theory of operation. For all constant region positions discussed in the present invention, numbering is according to the EU index in Kabat (Kabat et al., 1991, Sequences of Proteins of Immunological Interest [immunologically interesting protein sequence], 5th edition, United States Public Health Service, National Institutes of Health [US Public Health Service, National Institutes of Health], Bethesda, incorporated by reference in its entirety). Those skilled in the art of antibodies will appreciate that this convention consists of non-contiguous numbering of specific regions of the immunoglobulin sequence, thereby enabling standardization of references to conserved positions within the immunoglobulin family. Thus, the position of any given immunoglobulin as defined by the EU index will not necessarily correspond to its...
example 1
[0368] XmAb14045 treatment plan
[0369] This is a multicenter, open-label, multiple-dose, single-arm, phase 1, dose-escalation study of XmAb14045. Doses of XmAb14045 will be administered intravenously (IV) over a 2-hour infusion period. Dosage infusion periods may be altered based on any observed infusion toxicity.
[0370] This study will be conducted in 2 sequential parts (i.e. Part A and Part B).
[0371] Part A: Human subjects will be recruited into up to 8 consecutive dose cohorts (0.003, 0.01, 0.03, 0.075, 0.15, 0.3, 0.5 and 0.75 μg / kg) with an initial accelerated titration for the first 3 cohorts. The first 3 cohorts will each consist of 1 human subject until evidence of grade 2 toxicity, and the remaining cohorts will each enroll at least 3 human subjects into the classic 3+3 dose escalation regimen. Human subjects will be admitted for 3 days at the first and fourth dose (and if admission is necessary for cytokine / inflammatory cytokine collection at the 8 hour po...
example 2
[0403] In vitro antitumor efficacy
[0404] T cell-dependent cytotoxicity of XmAb14045 was examined against CD123 positive (KG1a and Kasumi-3) and CD123 negative (Ramos) cell lines using purified PBMC or T cell depleted PBMC as effector cells. Additionally, T cell activation was assessed by quantifying CD69 induction, a marker of lymphocyte activation, on CD4+ and CD8+ T cells. XENP13245 (anti-RSV x anti-CD3 bsAb) was used as a control. in CD4 + and CD8 + In T cells, XmAb14045 (but not XENP13245) displayed CD123 when human PBMC were supplied as the effector population + KG-1a (EC 50 0.28ng / mL; see Figure 8 ) and Kasumi-3 (EC 50 0.01 ng / mL) cell line and potent CD69 induction. However, when T cells were depleted from PBMC ( Figure 8 ), XmAb14045 failed to induce killing or induce CD69 expression on T cells. XmAb14045 does not induce CD123 - Cytotoxicity of the Ramos B cell line also did not induce T cell activation as measured by CD69 expression.
[0405] A serie...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More