Method and composition for diagnosis of melanocytic lesions

Abstract

This invention relates to monoclonal antibodies that recognize an antigen specific to melanocytic lesions. These antibodies are useful in methods of isolating melanoma cells and diagnosing melanocytic lesions. These antibodies are also useful for immunotherapy against melanoma.

Description

I. FIELD OF THE INVENTION [0001] This invention relates to melanoma-associated antigens, antibodies against melanoma-associated antigens, and diagnostic and therapeutic methods concerning melanoma. II. BACKGROUND OF THE INVENTION [0002] Human malignant melanoma usually starts as harmless moles that undergo radial to invasive growth and end in the destructive stage of metastatic melanoma. Melanoma usually resists chemotherapy and radiotherapy. Surgery is the most effective treatment. Early diagnosis is required for surgery to be effective, which is unfortunately hampered by the lack of markers that are sensitive and specific for melanoma. [0003] The commonly used antibodies for immuno-histochemical diagnosis of melanoma are HMB-45, anti-S-100 and NKI / C3 (for a review, please see Smoller B R, “Immunohistochemistry in the Diagnosis of Melanocytic Neoplasms”, in PATHOLOGY: State of the Art Reviews, 2:371-383, 1994). [0004] HMB-45 has been shown to react with the melanoma-associated anti...

AI Technical Summary

Benefits of technology

[0066] Pharmaceutical compositions suitable for use in the present invention include compositions wherein the active ingredients are contained in an effective amount to achieve its intended purpose. Determination of the effective amounts is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein. In addition to the active ingredients, these pharmaceutical compositions may contain suitable pharmaceutically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. Techniques for formulation and administration may be found in Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing Co., Easton, Pa. (1990). Suitable routes may include oral, rectal, transdermal, vaginal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections, just to name a few.

[0067] Preferred are pharmaceutical compositions for parenteral application. Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Additionally, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions. Exemplary compositions for intramuscular, subcutaneous or intravenous application include isotonic aqueous solutions or suspensions, optionally prepared shortly before use from lyophilized or concentrated preparations. The pharmaceutical compositions may contain agents for conserving, stabilizing, wetting, emulsifying or solubilizing the ingredients, salts for the regulation of the osmotic pressure, buffer and / or compounds regulating the viscosity (e.g., sodium carboxycellulose, sorbitol, dextran, polyvinylpyrrolidine or gelatine). They are prepared by methods known in the art, e.g. by conventional mixing, dissolving or lyophilizing, and contain from about 0.01% to about 50% of active ingredients. The compositions for injections are processed, filled into ampoules or vials, and sealed under aseptic conditions according to methods known in the art.

[0068] The specific mode of administration and the dosage will be selected by the attending physician taking into account the particulars of the patient, the state of the disease, the type of melanoma treated, and the like. It should be noted that the attending physician would know how to and when to terminate, interrupt, or adjust administration due to toxicity, or to organ dysfunctions. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response were not adequate (precluding toxicity). The magnitude of an administrated dose in the management of the disorder of interest will vary with the severity of the condition to be treated and to the route of administration. The severity of the condition may, for example, be evaluated, in part, by standard prognostic evaluation methods. Further, the dose and perhaps dose frequency, will also vary according to the age, body weight, and response of the individual patient. A program comparable to that discussed above may be used in veterinary medicine.

Problems solved by technology

Early diagnosis is required for surgery to be effective, which is unfortunately hampered by the lack of markers that are sensitive and specific for melanoma.

However, anti-S100 antibodies are notoriously unspecific.

These unspecific activities limit the usefulness of NKI / C3 antibody in the diagnosis of melanocytic lesions.

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