Unique Patient Neo-Peptides To Fight Cancer
2019 John A. Catanzaro
Over my 22 years as a physician specializing in personalized cancer treatment, I have worked tirelessly in innovating a better form of cancer treatment that would support my patients diagnosed with a variety of end-stage cancers. The innovation included isolating molecular products from tumor, urine, lymph fluid, lung fluid, CSF and serum in cases that were in various stages and with different system compartments involved.
Most of my patients failed first-line chemotherapeutic and even targeted biological treatments and were left with no other hopeful solutions. I made it my focus to place all of my effort on treating the patient and not trying to come up with some lofty new research design and drug. However, I utilized all venues to innovate a unique patient design. The aim was not to develop a new drug but a precision-based innovation to assist in immune surveillance and defense. However, the process was indeed developing a precision-based neo-peptide / antigen derived from the patient’s own immune information system.
Molecular Typing and HLA Matching
Simply, I sent my patient samples for molecular typing, simultaneously utilizing whole exome sequencing and peptide sequence typing. In addition I typed every patient’s HLA expression using high resolution classification A,B and C. My rationale and theory was to use rejection genetics to initiate immunogenic antigen response in my patients that had tumor escape, evasion and aggressive mutations.
After all the patient typing was complete, utilizing unique bioinformatics and data mining with specific focus on cancer and peptide databases was then achieved. A complete data mapping was achieved matching every unique peptide sequence /antigen isolated from the patient samples and then a matching of the top peptides / antigens with extensive HLA matching to determine what segments of the molecular product (peptide sequence) was the hottest immunogenic match for the patient within the classification. The focus was upon cancer related peptide sequences isolated and the HLA-A, B ,C (MHC Class I category) match. The average peptide sequences chain length was between 8–16 peptides of the specific cancer related protein isolated and analyzed. The main areas of focus is the patient’s active immune defense rather than passive immune centered innovations. However, considerations in passive immune defense innovations was also explored with these patients as well.
All of my patients with similar cancers were matched and selection criteria of the HLA matches included the relation to the molecular relationship to the expressed cancer / cell / tumor and what was also seen in the research literature and general cancer population data inquiry of the specific cancer type and then analyzed and matched for the final selection of the specific peptide sequences. Similar molecular protein expression unique to the cancer type, mutation, migration and metastasis were seen in >80% of my patients that were typed. HLA Classification
Development of the Unique Neo-Peptides / Antigens
Unique patient sequenced peptides of the highest immunogenic match to the expressed cancer and HLA typing (based upon patient mapping) were then synthesized. A single patient could have anywhere from six to fourteen different cancer typed poly-peptide sequences as part of their vaccine pool. The vaccine pool final product was suspended in a vaccine nano-carrier adjuvant (bio-lipid shark oil medium) for immunogenic delivery. The end product was tested for viability, sterility and quality.
Vaccine Administration and Defense Cell Training
Isolation of the patient’s immune defense and regulatory cells including CD34, CD303, CD304, CD56, CD16, CD4, CD8 and CD25 were isolated and grown in fortified culture for seven days and electroporated with the unique polypeptide pool. After the growth period of seven days cultures were tested for viability, sterility and quantity. Simultaneously, the patient had the polypeptide vaccine pool administered as a subcutaneous injection for 10 days. After the 10 day vaccine induction the cultured cells processed with the polypeptides were administered over a 5 day infusion period in sequence.
Within 12 weeks of administration of the vaccine pool and infusions patients experienced mild fatigue, mild rash at site of injection and elevated total WBC count for 14–21 days. In some cases, the vaccine regimen and infusion were repeated three times within a 12 month period in high resistant cancers with impressive outcomes. Cancer markers, inflammation markers, and tumors began to normalize and regress and patients experienced improvement in energy and vitality. Many patients have reached a 10 year survival and are completely tumor / cancer free.
Immunocentric innovations should be considered as a primary treatment delivery method while a patient’s disease is expressed. However, it is essential that typing and unique matching be achieved. Chemotherapeutic agents are known for cytotoxic and multi-organ system effects. We are discovering target specific agents and pulsed delivery is a less toxic regimen. Coordinated regimens of this type can be co-administered with greater efficacy. However, give the immune defenses a chance and they will work. From concept to bottling and delivery of the end product, including all the matching and analysis, was an average of 30 days.