Monoclonal antibodies against loricrin

A method for determining a treatment regime for a subject suffering from melanoma, the method comprising:

• (i) determining the expression of Loricrin in a tissue sample obtained from the subject by contacting the tissue sample with a monoclonal antibody against Loricrin and visualizing the antibody in the tissue sample with a reagent that generates a detectable signal, wherein the tissue sample comprises tissue overlying a primary melanoma;
• and
• (ii) comparing the expression obtained in (i) with a reference tissue or levels obtained therefrom, and
• (iii) (a) if expression of Loricrin is normal, following a normal recognized care pathway, or
• (iii) (b) if expression of Loricrin is decreased or lost, treating the subject with a systemic anti-cancer treatment regime,
• wherein the antibody against Loricrin comprises the following complementarity determining regions (CDRs):
• (a) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 22;
• (b) HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 23;
• (c) HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 24;
• (d) LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 25;
• (e) LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 26;
• and
• (f) LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 27.

A method of treating a subject suffering from melanoma, the method comprising:

• (i) determining the expression of Loricrin in a tissue sample obtained from the subject by contacting the tissue sample with a monoclonal antibody against Loricrin and visualizing the antibody in the tissue sample with a reagent that generates a detectable signal, wherein the tissue sample comprises tissue overlying a primary melanoma;
• and
• (ii) comparing the expression obtained in (i) with a reference tissue or levels obtained therefrom, and
• if there is a decrease in the expression of Loricrin in the tissue sample compared to the reference tissue or levels, or a loss of expression of Loricrin, administering a therapeutic agent to the subject
• wherein the antibody against Loricrin comprises the following complementarity determining regions (CDRs):
• (a) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 22;
• (b) HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 23;
• (c) HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 24;
• (d) LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 25;
• (e) LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 26;
• and
• (f) LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 27.

A method of treating a subject suffering from melanoma, the method comprising administering a therapeutic agent to the subject, wherein the subject has been identified as having decreased or a loss of expression of Loricrin after determining the expression of Loricrin in a tissue sample obtained from the subject by contacting the tissue sample with a monoclonal antibody against Loricrin and visualizing the antibody in the tissue sample with a reagent that generates a detectable signal, wherein the antibody against Loricrin comprises the following complementarity determining regions (CDRs):

• (a) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 22;
• (b) HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 23;
• (c) HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 24;
• (d) LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 25;
• (e) LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 26;
• and
• (f) LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 27, wherein the method is for inhibiting metastasis or decreasing the risk of metastasis in the subject.

An in vitro assay for predicting an increased risk of metastasis in a subject suffering from melanoma, the assay comprising:

• contacting a tissue sample obtained from the subject with an antibody against Loricrin, wherein the antibody against Loricrin comprises the following complementarity determining regions (CDRs):
• (a) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 22;
• (b) HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 23;
• (c) HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 24;
• (d) LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 25;
• (e) LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 26;
• and
• (f) LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 27,
• wherein the tissue sample comprises tissue overlying a primary melanoma and the presence of Loricrin creates an Loricrin-antibody complex;
• and
• detecting and/or quantifying the Loricrin-antibody complex, wherein optionally:
• (ai) the tissue sample comprises at least a portion of a peri-tumoral epidermis overlying the primary melanoma and the Loricrin-antibody complex is detected in the in the stratum corneum of the epidermis;
• and/or
• (bi) the Loricrin-antibody complex is detected and/or quantified by visual assessment or by an automated slide scanner.

A kit for predicting an increased risk of developing metastasis of a subject suffering from melanoma, the kit comprising an antibody against Loricrin, wherein the antibody against Loricrin comprises the following complementarity determining regions (CDRs):

• (a) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 22;
• (b) HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 23;
• (c) HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 24;
• (d) LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 25;
• (e) LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 26;
• and
• (f) LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 27,
• wherein optionally the kit further comprises at least one capture agent, wherein the at least one capture agent comprises a detection moiety and/or a binding moiety specific for the antibody against Loricrin.