The list of tumor cell ANTIGENS against which the vaccine RESAN is directed to act upon

The antitumor vaccine RESAN contains imitators of mainly three major groups of tumor antigens due to which it acts as cancer vaccine triggering immune responses against wide types of tumors. The three groups of tumor antigens against which the vaccine RESAN is directed to act upon are:

1. 22 peptide fragments of the Homo sapiens telomerase ferment (hTRT);
2. Cytokeratin-19 (CYFRA21-1);
3. Peptide fragments of 40 most common cancer specific antigens.

1. Homo sapiens telomerase ferment (hTRT)
Homo sapiens telomerase reverse transcriptase (hTRT) is a tumor-associated antigen expressed in the vast majority of human tumors and is presently one of the most promising target candidates for a therapeutic cancer vaccine [22, 23, 24, 25]. (This enzyme is in silent/inactive in normal tissues except in some body cells-like stem cell, basal cells of epidermis, male and female reproductive cells but it is most active in more than 85% of the cancer cells) [24].

It is this very enzyme, which enables the cancer cells to under go endless cell divisions. The fragments of this enzyme in complex with HLA molecules are located on the cancer cell membranes. The vaccine RESAN, in its basic composition, include glycoproteins which are analogous to 22 peptide fragments of the telomerase enzyme (hTRT). Due to this, the vaccine possesses a broad spectrum of antitumor activities.

In the amino acidic sequence of hTRT (Table 1), the peptide fragments are shown in orange colour which are present in the vaccine RESAN (the international single-letter designation of amino acids is illustrated).

The administration of vaccine RESAN in an organism triggers the immune mechanism to form specific antitumoral T-lymphocytes (CTLs) against the cells with active telomerase enzyme i. e. cancer cells. The specific antitumoral T-lymphocyte recognizes the tumor peptides (each with 8-10 amino acids) represented in a complex HLA class I molecule on the cancer cell membranes and destroy them.

2. Cytokeratin fragment 19 (CYFRA 21-1)
Most of the malignant tumors are hard in consistency. This is due to the presence of a strong cellular structure known as the cytoskeleton, which consists of proteins – cytokeratins. There are more than 20 known types of cytokeratins. For example – the cytokeratin fragment 19 is located in many of the epithelial malignant cells. With the help of these strong cytokeratins, the cancer cells displace the normal cells invading new spaces for their growth into the healthy tissues.

In a healthy person the concentration of cytokeratin-19 in blood serum may deviate from 0.1 to 3.3 ng/mL; thus the normal (average) concentration of cytokeratin-19 is considered as 2.1 ng/mL [21]. Today the cytokeratins-19 test is used as a standard tumor marker for the diagnosis of metastatic growths of cancers from epithelial cells; this tumor marker has been found elevated in different types of epithelial cancers: prostate cancers [1], hepatocellular carcinoma [2, 3, 4], pancreatic carcinoma [5, 6], breast cancer [7, 8, 9], ovarian adenocarcinoma [10, 11], basal cell carcinoma [12], thyroid tumors [13], colorectal cancer [7, 14], squamous cell carcinoma of head and neck [7, 15], neoplastic lymphadenopathies [20], lung carcinoma [7, 17, 18, 19, 20].

The vaccine RESAN is the first cancer vaccine, which contains, in its chemical composition, the imitators of the protein fragments of the cellular cytoskeleton located in the malignant tumors. With the help of Enzyme-Linked Immunosorbent Assay (ELISA) kit (Hoffman-La Rosch CYFRA 21-1), it was determined that in a single vial of the vaccine RESAN (200 mg) the concentration of the cytokeratin-19 was 20 times higher than in the blood serum of a healthy person. This allows us to use the vaccine to trigger specific antitumor immune responses against various types of human epithelial tumors. Thus, the presence of the cytokeratin-19 imitators in the vaccine composition is one more important factor, which makes it "a cancer vaccine of wide spectrum".

3. Peptide fragments of 40 most common cancer specific antigens
In order to intensify and widen the spectrum of the anti tumor immune responsing capacity of the vaccine even more, other additional glycoproteins are included in the composition of vaccine RESAN whose (glycoproteins) peptide fragments are analogous to some particular fragments of 40 most common cancer antigens (Table 2).

Table 2.

These glycoproteins included in the composition of the vaccine imitate 6-50 different peptide fragments (each with 7-30 amino acids) of each cancer antigens illustrated above.