Isolation of tumoricidal human factors from lymphoid cells and enzymatic digestion of these factors into small fragments retaining tumoricidal effects.
Gel filtration and immunoadsorption techniques have been utilized to purify tumoricidal factors from sturgeon sera as well as human plasma. Two pure proteins with cytotoxic activity were isolated from the sturgeon serum (factors A2 and B2) and two additional cytotoxic factors were isolated from human plasma (Factors A and B). In another study, human factors A and B were quantitated in both normal donor and cancer patients' plasma. It was found that the cancer patients produced at least 50% less tumoricidal factors than did the normal donors. Furthermore, when the secretions from various lymphoid cell populations were purified utilizing immunoadsorbent techniques, it was found that the macrophages generally were producing the human tumoricidal factors. Both the sturgeon and the human factors were enzymatically cleaved into several small molecular weight fragments. Sephadex G-75 column chromatography was then utilized to isolate the enzymatic cleavage fragments. Three fragments with cytotoxic activity were isolated from both sturgeon factor A2 and B2. Similarly, human factor A was digested into two fragments with cytotoxic activity and factor B was digested into three fragments with cytotoxic activity. The molecular weights of the cytotoxic sturgeon and human fragments ranged from 14,000 to 23,000 whereas the intact sturgeon and human factors had a molecular weight slightly greater than 67,000. Ultimately, if these small molecular weight fragments can be sequenced, then it would be possible to prepare a synthetic analog which might have future potential as a mode of treatment for cancer patients.
D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D002460:Cell Line; D003114:Colony-Forming Units Assay; D003603:Cytotoxins / Q000032:analysis* / Q000627:therapeutic use; D004591:Electrophoresis, Polyacrylamide Gel; D005399:Fishes / Q000097:blood; D006801:Humans; D007962:Leukocytes / Q000032:analysis*; D008297:Male; D008970:Molecular Weight; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy; D010206:Papain; D011471:Prostatic Neoplasms; D014410:Tumor Stem Cell Assay
D001798:Blood Proteins; D003603:Cytotoxins; D010206:Papain