Compositions and methods for modulating cellular internalization

A method for modulating cellular internalization, the method comprises administering to a cell an engineered antibody or functional fragment thereof comprising:

• a first antigen binding moiety capable of binding to a cell-surface guide antigen having a first rate of cellular internalization;
• and
• a second antigen binding moiety capable of binding to a cell-surface effector antigen having a second rate of cellular internalization,
• wherein the internalization property of the engineered antibody or functional fragment thereof is determined by a relative surface density ratio of the guide antigen to the effector antigen, and
• wherein one of the two cellular internalization rates is at least 50%, at least 70%, at least 80%, or at least 90% greater than the other rate.

A method for modulating cell-type selective signaling in a subject, the method comprises administering to the subject an engineered antibody or functional fragment thereof comprising:

• a first antigen binding moiety capable of binding to a cell-surface guide antigen, wherein the guide antigen is expressed in the subject in a cell-type selective manner and has a first rate of cellular internalization;
• and
• a second antigen binding moiety capable of binding to a cell-surface effector antigen having a second rate of cellular internalization,
• wherein the internalization property of the engineered antibody or functional fragment thereof is determined by a relative surface density ratio of the guide antigen to the effector antigen;
• and
• wherein one of the two cellular internalization rates is at least 50%, at least 70%, at least 80%, or at least 90% greater than the other rate.

A method for treating a health condition or disease in a subject in need thereof, the method comprises administering to the subject a therapeutically effective amount of an engineered antibody or functional fragment thereof comprising:

• a first antigen binding moiety capable of binding to a cell-surface guide antigen having a first rate of cellular internalization;
• and
• a second antigen binding moiety capable of binding to a cell-surface effector antigen having a second rate of cellular internalization,
• wherein the internalization property of the engineered antibody or functional fragment thereof is determined by a relative surface density ratio of the guide antigen to the effector antigen;
• and
• wherein one of the two cellular internalization rates is at least 50%, at least 70%, at least 80%, or at least 90% greater than the other rate.