Racotumomab (trade name Vaxira) is a therapeutic

cancer vaccine A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as ''therapeutic'' cancer vaccines or tumor antigen vaccines. Some of the vaccines ...

for the treatment of solid tumors that is currently under clinical development by ReComBio (R and Research in Computational Biology), an international public-private consortium with the participation of the Center of Molecular Immunology at

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(CIM) and researchers from Buenos Aires University and

National University of Quilmes The National University of Quilmes (, UNQui) is an Argentine national university and the most important one in the Quilmes area. The National University of Quilmes was founded on October 23, 1989. Located in Bernal ( Quilmes County), it serves th ...

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. It induces the patient's immune system to generate a response against a cancer-specific molecular target with the purpose of blocking tumor growth, slowing disease progression and ultimately increasing patient survival. Racotumomab triggers an immune response against the tumor antigen N-glycolyl (NGc) GM3 (NGcGM3), a type of

ganglioside A ganglioside is a molecule composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (e.g. N-acetylneuraminic acid, ''N''-acetylneuraminic acid, NANA) linked on the sugar chain. NeuNAc, an acetylated derivative ...

present on the cell surface of malignant cells from lung and breast, melanoma, as well as neuroectodermal pediatric tumors. Racotumomab has successfully completed a proof-of concept clinical trial in advanced non-small cell

lung cancer Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...

(NSCLC) and is currently being tested in a large, multinational study for the same indication. Racotumomab has been approved in two countries, Argentina and Cuba, for the treatment of recurrent or advanced NSCLC, or NSCLC independent of the disease stage when no other standard therapy can be administered.

Medical uses

Racotumomab is administered in patients who have previously received the oncospecific treatment established in the oncological therapeutic standards (surgery, chemotherapy and radiation therapy). A racotumomab-

alum An alum () is a type of chemical compound, usually a hydrated double salt, double sulfate salt (chemistry), salt of aluminium with the general chemical formula, formula , such that is a valence (chemistry), monovalent cation such as potassium ...

solution is administered by

intradermal injection Intradermal injection (also intracutaneous or intradermic, abbreviated as ID) is a shallow or superficial injection of a substance into the dermis, which is located between the epidermis and the hypodermis. For certain substances, administration ...

every 14 days for the first 2 months (5 doses), followed by monthly booster doses.

Pharmacology

Mechanism of action

Gangliosides are concentrated on the surface of mammalian cells and play an important role in cell growth and differentiation. NGc gangliosides, however, are practically undetectable in healthy human tissues and fluids due to a genetic deletion in the human gene that encodes the enzyme responsible for the synthesis of NGc, the CMP-N-acetyl hydroxylase. Nonetheless, the NGcGM3 ganglioside is highly expressed in several human cancers, including lung, breast, melanocytes, colon and neuroectodermal pediatric tumors, making this neoantigen an attractive target for cancer therapy. Racotumomab is an anti-idiotypic mouse

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

that mimics NGc gangliosides, thus triggering an immune response against the tumor antigen NGcGM3. Therefore, rather than being a passive antibody therapy, Racotumomab acts as a therapeutic vaccine. In melanoma, breast, and lung cancer patients, Racotumomab was able to elicit a specific immune response that recognized and directly killed tumor cells expressing the neoantigen by a mechanism of oncotic necrosis. The specific expression of NGcGM3 in malignant cells reduces the potential risk of an immune cross-reactivity that could cause serious adverse effects.

Adverse effects

Racotumomab is well tolerated by patients. The overall toxicity of the vaccine has been classified as grade 1 and 2, according to the NCI

Common Toxicity Criteria The Common Terminology Criteria for Adverse Events (CTCAE), formerly called the Common Toxicity Criteria (CTC or NCI-CTC), are a set of criteria for the standardized classification of adverse events of drugs and treatment used in cancer therapy. ...

(version 3.0). Treatment is mostly associated with mild to moderate

injection site reaction Injection site reactions (ISRs) are reactions that occur at the site of injection of a drug. They may be mild or severe and may or may not require medical intervention. Some reactions may appear immediately after injection, and some may be delayed ...

s (local erythema, induration and pain), which disappear within 24–48 hours. Systemic reactions, such as flu-like symptoms and chills are less frequent, reversible, and self-limited.

History

Clinical trials

A randomized, multicenter, phase III study of active specific immunotherapy with Racotumomab plus best support treatment, versus best support treatment in patients with advanced NSCLC who have achieved an objective response (partial or complete) or stable disease with standard first-line treatment is underway in Argentina, Brazil, Cuba, Indonesia, Philippines, Singapore, Thailand and Uruguay. 1,082 patients with NSCLC in stages IIIA (non-resectable), IIIB or IV will be evaluated in the study. The study is sponsored by Recombio in collaboration with Elea Laboratories (Argentina), CIM (Cuba), Europharma Laboratories (Brazil), Innogene Kalbiotech (Singapore) and several public research institutions.

References

{{monoclonals for tumors Monoclonal antibodies Cuban inventions