The present invention is directed to bi-specific diabodies that comprise two or more polypeptide chains and which possess at least one
Epitope-
Binding Site that is immunospecific for an
epitope of PD-1 and at least one
Epitope-
Binding Site that is immunospecific for an
epitope of
LAG-3 (i.e., a “PD-1×
LAG-3 bi-specific diabody”). More preferably, the present invention is directed to bi-specific diabodies that comprise four polypeptide chains and which possess two
Epitope-Binding Sites that are immunospecific for one (or two)
epitope(s) of PD-1 and two Epitope-
Binding Site that are immunospecific for one (or two) epitope(s) of
LAG-3 (i.e., a “PD-1×LAG-3 bi-specific,
tetra-valent diabody”). The present invention also is directed to such diabodies that additionally comprise an
immunoglobulin Fc Domain (“bi-specific Fc diabodies and bi-specific,
tetra-valent, Fc diabodies”). The diabodies of the present invention are capable of simultaneously binding to PD-1 and to LAG-3, particularly as such molecules are arrayed on the surfaces of human cells. The invention is directed to pharmaceutical compositions that contain such diabodies, and to methods involving the use of such diabodies in the treatment of
cancer and other diseases and conditions.