Increase of the antitumour efficacy of the biocompound IMMUNEPOTENT CRP by enzymatic treatment

Abstract

IMMUNEPOTENT CRP is a dialyzable leukocyte extract obtained from bovine spleen with immunomodulatory and antitumour properties; therefore, when administrated as an adjuvant therapy for cancer patients, it has increased their survival and quality of life. The bioavailability of any orally administered compound can be reduced due to gastrointestinal enzymes. In this study, we evaluated if IMMUNEPOTENT CRP is resistant to the treatment with different enzymes (proteases, nucleases, polysaccharide-degrading enzymes or lipase), using as parameters for biological activity measurement its in vitro antitumour and antioxidant properties and in vivo the antitumour effect of IMMUNEPOTENT CRP treated with proteinase K. In conclusion, we consider necessary to include the antioxidant and cytotoxic activity on the MCF-7 cancer cell line as parameters for the quantitative determination of biological activity or potency tests for batch release. Additionally, the results showed that different enzymatic treatments do not affect the antitumour and antioxidant activities of IMMUNEPOTENT CRP in vitro, suggesting that this product can be administered orally without any loss of biological activity. Furthermore, IMMUNEPOTENT CRP treatment with proteinase K increases the antitumour activity in vivo.

Air Pouch Model: An Alternative Method for Cancer Drug Discovery

“…We induced the air pouch model, inoculated L5178Y-R cancer cells, and determined if our compound interfered with tumor implantation. We concluded that our bio-compound has antitumor properties [59].…”

Bovine Dialyzable Leukocyte Extract IMMUNEPOTENT-CRP Induces Selective ROS-Dependent Apoptosis in T-Acute Lymphoblastic Leukemia Cell Lines

“…Similar treatments for leukemia have been difficult to find because this being a cancer of the immune system and it is unclear whether the drugs will distinguish between healthy and cancerous cells [10]. I-CRP shows selective cytotoxicity to solid cancer cells [16,20,21,23], such as MCF-7, BT-474, MDA-MB-453, A-427, Calu-1, U937, and L5178Y-R cell lines [20,21,23]. Other types of DLE have also shown antitumor activity in prostate cancer [29] and can be used in combination with chemotherapies [30] and with antibiotics as manumycin in mouse breast cancer (4T1) [31].…”

“…IMMUNEPO-TENT-CRP© (I-CRP) is an immunotherapeutic agent composed of bovine dialyzable leukocyte extract (bDLE) obtained from disintegrated spleen. In previous reports, I-CRP showed a potential immunomodulatory effect in preclinical trials of breast cancer treatments, [14,15] and in in vivo assays, it showed an antitumor effect [16,17]. Several in vitro studies reveal its immunomodulatory properties in human and mouse monocytes and macrophages [18,19] and their cytotoxic effect in different cancer cell lines [20,21].…”

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“…Besides its chemo-protective activity, IMMUNEPOTENT CRP has cytotoxic effect against several cancer cell lines, including MCF-7, BT-474, MDA-MB-453 (breast cancer) , A-427, Calu-1 (lung cancer) , U937 (leukemia) , and L5178Y (lymphoma) [13], B16F10 (melanoma) [14], K562, MOLT-3 (human leukemia) [15], and HeLa (cervical cancer) [16] in vitro; also, toxic doses for cancer cells do not affect human PBMC [13] human monocytes, and murine peritoneal macrophage [15]. Furthermore, IMMUNEPOTENT CRP possesses antitumor activity against murine lymphoma [16] and melanoma [17] in a dose-dependent manner. The search for novel drugs is still a priority goal for cancer therapy due to the inefficiency, high toxicity, adverse effects and development of resistance to chemotherapeutic drugs.…”

“…Higher doses caused too much discomfort and severe pain. It is reasonable to assume that this is the reason why complete tumor regression was not achieved in the murine models [16,17]. On the contrary, with 50 units administrated to dogs by the intravenous route, there are no signs of discomfort or pain [data not published yet].…”