(CHAPERONE RICH CELL LYSATE)
Chaperone Rich Cell Lysate (CRCL) is a source of patient-specific tumor antigens. CRCL is derived from a sample of a patient's own tumor cells. The chaperone proteins within tumor cells carry autologous tumor-specific peptides (antigens) which are capable of conferring tumor-specific immunity that is customized to the patient's own tumor. A unique feature of CRCL is that the chaperone proteins that carry the antigens also serve as an adjuvant.
CRCL consist of a large numbers of tumor antigens, which increases the chance of an effective immune response to develop against all the tumors in the body. Vaccines that contain only a single tumor antigen (or a limited number of antigens) are common, but these type of vaccines are thought to be inferior to those which contain multiple antigens. This is because when an immune response is directed to only a single antigen, the tumor cells can simply hide the one selected antigen to avoid the immune attack. In addition, individual tumor cells can express different antigen fingerprints.
While one tumor cell may express the selected antigen, others may not. This could lead to an immune response which destroys some tumors, but leaves other tumor cells untouched. The untouched tumor cells are resistant to immune attack because they do not express the target antigen of the vaccine. In this situation, tumor cells which have evaded immune attack will grow and spread even though a patient has been successfully vaccinated. This is the reason for failure of many single antigen and limited antigen anti-tumor vaccines that have been tested in the clinic.
CRCL has been shown to contain innumerable tumor antigens. CRCL is prepared from lysates of surgically resected or biopsy-derived tumor samples collected from a patient at the point-of-care. The tumor cells are lysed in the laboratory and the chaperone proteins which resided inside the tumor cells are purified from the lysed tumor cells. The chaperone proteins in theory contain the whole repertoire of tumor antigens which identify the tumor to the immune system, making it difficult for the tumor to evade an immune attack after successful vaccination.
The mixture of chaperone proteins includes calreticulin, hsp70, hsp90 and glucose-regulated protein 94/glycoprotein 96 (grp94/gp96), each which are known to be capable of chaperoning a variety of antigens. The final enriched CRCL protein mixture is tested to assure presence of hsp70, which is known to co-migrate with the other chaperone proteins and serves as a marker for their presence. This quality control test assures that each vaccine prepared from a patient's own tumor contains the required components.
CRCL is supplied in multiple single dose vials. Prior to use, the individual vial is removed from frozen storage and kept at room temperature until thawed. The contents of the CRCL vial are then drawn aseptically into a syringe for patient administration. CRCL is for intradermal injection only.
Tumor-derived chaperone-rich cell lysate (CRCL) is a potent, personalized anti-cancer vaccine isolated from tumor tissue. CRCL consists of numerous chaperone/heat shock proteins, including the highly immunogenic Hsp70, Hsp90, glucose regulated protein 94, and calreticulin. CRCL provides both a source of tumor antigens and danger signals triggering antigen presenting cell activation.