NOVELTY - A pre-targeting system comprising an anti-cluster of differentiation (CD)38 single-domain antibody (sdAb) and a second agent capable of specifically binding to the anti-CD38 sdAb and comprising a second molecule is new, where the antibody comprises an amino acid sequence that comprises 3 complementary determining regions (CDR1-CDR3). The CDR1 is chosen from (a) an amino acid sequence of SEQ ID NO: 1, (b) polypeptides that have at least 80% amino acid sequence identity with SEQ ID NO: 1, and (c) polypeptides that have 3, 2 or 1 amino acid difference with SEQ ID NO: 1. The CDR2 is chosen from (a) an amino acid sequence of SEQ ID NO: 2, (b) polypeptides that have at least 80% amino acid sequence identity with SEQ ID NO: 2, (c) polypeptides that have 3, 2 or 1 amino acid difference with SEQ ID NO: 2.

USE - The pre-targeting system is useful in kit of parts or medicine or diagnostics for diagnosing, monitoring and treating neoplastic disease in subject, and evaluating or monitoring presence, location and/or amount of CD38-expressing cells in subject. The neoplastic disease is a solid tumor. The neoplastic disease is hepatocellular carcinoma, lung cancer, melanoma, breast cancer or glioma, preferably hematological malignancy. The neoplastic disease is multiple myeloma, non-Hodgkin lymphoma (NHL) or chronic lymphoid leukemia (CLL), preferably multiple myeloma (all claimed).

ADVANTAGE - The system exhibits excellent cytotoxic effect on CD38-expressing neoplastic cells.

DETAILED DESCRIPTION - A pre-targeting system comprising an anti-cluster of differentiation (CD)38 single-domain antibody (sdAb) and a second agent capable of specifically binding to the anti-CD38 sdAb and comprising a second molecule is new, where the antibody comprises an amino acid sequence that comprises 3 complementary determining regions (CDR1-CDR3). The CDR1 is chosen from (a) an amino acid sequence of SEQ ID NO: 1, (b) polypeptides that have at least 80% amino acid sequence identity with SEQ ID NO: 1, and (c) polypeptides that have 3, 2 or 1 amino acid difference with SEQ ID NO: 1. The CDR2 is chosen from (a) an amino acid sequence of SEQ ID NO: 2, (b) polypeptides that have at least 80% amino acid sequence identity with SEQ ID NO: 2, (c) polypeptides that have 3, 2 or 1 amino acid difference with SEQ ID NO: 2. The CDR3 is chosen from (a) a 18 amino acid sequence (SEQ ID NO: 3) fully defined in the specification, (b) polypeptides that have at least 80% amino acid sequence identity with SEQ ID NO: 3, and (c) polypeptides that have 3, 2 or 1 amino acid difference with SEQ ID NO: 3. Tyr-Thr-Asp-Ser-Asp-Tyr-Ile (SEQ ID NO: 1), and Thr-Ile-Tyr-Ile-Gly-Gly-Thr-Tyr-Ile-His (SEQ ID NO: 2).

INDEPENDENT CLAIMS are included for the following:

• kit of parts comprising the pre-targeting system;
• use of pre-targeting system or kit of parts in medicine or diagnostics for diagnosing, monitoring and treating a neoplastic disease in a subject; and
• imaging method for evaluating or monitoring presence, location and/or amount of CD38-expressing cells in a subject involves (i) detecting, in a subject to whom a detectable quantity of the pre-targeting system, and (ii) generating an image representative of the location and/or quantity or intensity of the signal, where the second agent comprises a signal-emitting molecule, has been administered, signal emitted by said signal-emitting molecule.