Immunomodulatory peptides and methods for modulating the immune system in a subject
Inventors
Travassos, Luiz Rodolpho Raja Gabaglia
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11479604-B2
Publication Date
2022-10-25
Expiration Date
Abstract
Peptides have immune system modulation properties. The immunologically active peptides can be derived from the heavy-chain complementarity determining region-3 of a humanized monoclonal antibody to NaPi2B transporter. Such peptides can be used to modulate the immune system of a subject under cancer treatment.
Core Innovation
The invention relates to immunomodulatory peptides derived from the VH CDR3 region of a humanized monoclonal antibody to the NaPi2B transporter. Exemplary peptides include Rb9 (SEQ ID 1), Rb10 (SEQ ID 3), and Rb9-MID (SEQ ID 2), and the peptides are used to modulate immune responses in a subject having cancer or being under cancer treatment.
A central concept is contacting dendritic cells with an effective amount of a peptide derived from the VH CDR3 of a humanized antibody to NaPi2B, specifically Rb9 (SEQ ID No. 1), and then administering the peptide-treated dendritic cells to modulate the immune system. The document further describes effects on human monocyte-derived dendritic cells (mo-DC), including correcting dendritic cell functional bias and enhancing T cell induction.
The invention also encompasses context-dependent modulation of dendritic cell activation states, including inhibition of over-stimulated dendritic cells, stimulation of poorly activated or suppressed dendritic cells, and balancing of dendritic cells with no functional alteration. Mechanistic assertions described include that Rb9 binds MIF and CD74 and modulates the MIF/CD74 signaling axis, and that PEGylation (PEG-Rb9) can increase antitumor activity, with antitumor protection demonstrated in immune-competent animals.
Claims Coverage
The provided independent claims cover two main approaches: ex vivo dendritic-cell contact followed by administration to modulate the immune system in a cancer subject, and ex vivo dendritic-cell treatment to treat the dendritic cells of a cancer subject. Across the independent claims, the inventive coverage centers on using the VH CDR3-derived peptide Rb9 (SEQ ID No. 1) from a humanized antibody to NaPi2B for dendritic-cell modulation.
Ex vivo contacting dendritic cells with a NaPi2B VH CDR3 peptide then administering them
Contacting dendritic cells of the subject ex vivo with an effective amount of a peptide derived from the VH CDR3 of a humanized antibody to NaPi2B, wherein the peptide is Rb9 (SEQ ID No. 1), and administering the dendritic cells to the subject to modulate the immune system.
Treating dendritic cells ex vivo using a NaPi2B VH CDR3 peptide
Contacting dendritic cells of a subject ex vivo with a peptide derived from the VH CDR3 of a humanized antibody to NaPi2B to thereby treat the dendritic cells of the subject, wherein the peptide is Rb9 (SEQ ID No. 1), with the subject having cancer or being under cancer treatment.
Overall, the claim set is directed to ex vivo dendritic-cell contact/treatment using the VH CDR3-derived NaPi2B peptide Rb9 (SEQ ID No. 1), coupled either with subsequent administration to modulate the immune system or to treat the dendritic cells as part of cancer treatment.
Stated Advantages
Modulating the immune system of a subject having cancer or being under cancer treatment.
Enhancing T cell induction (as described in refinements to the independent claim).
Correcting dendritic cell functional bias (as described in the provided claim refinements/summary).
Inhibiting over-stimulated dendritic cells and stimulating poorly activated or suppressed dendritic cells, while balanced dendritic cells undergo no functional alteration (as described in the provided dependent refinements).
Inhibition/stimulation/balancing of dendritic cell activation states (as described in the provided claim refinements/summary).
Documented Applications
Cancer patients/subjects under cancer treatment, including melanoma, by modulating immune responses through dendritic cells contacted ex vivo with Rb9 (SEQ ID No. 1).
Human monocyte-derived dendritic cells (mo-DC) contexts and outcomes associated with T cell induction and dendritic-cell activation-state modulation.
Antitumor protection demonstrated in immune-competent animals (not in immunodeficient animals).
Interested in licensing this patent?