Despite all the progresses made in cancer detection and treatment, it remains one of the most deadly diseases. Developing effective treatment of late stage cancer has been our biggest dream since we made the discovery of the observable adjuvant effect of PICKCa at Franch Paster Institut in 1993   . After over 30 years of research, we developed a noncytotoxic anti-cancer drug named Pamica (PICNH2Ca2), which is the second generation product of PICKCa. Preliminary clinical trial results suggested that Pamica is both safe and effective in treating late stage cancer with markedly improved life quality and prolonged survival. Except for a few cases of local pain near the injection site, no other side effects have been observed.
2. Experimental Section
2.1. The composition of Pamica (PICNH2Ca2)
Pamica is a double-stranded RNA drug. It consists of dsRNA polyI:C, non-anti- biotic amino compounds and CaCl2. These constituents are bonded together organically rather than simply mixed. The main difference between Pamica and PICKCa is that Pamica substitutes non-antibiotic amino compounds for kanamycin in PICKCa. Being non-antibioticamino compounds with more amino groups to combined with phosphate group in PolyI:C, these compounds are both safe and more effective in Pamica than kanamycin in PICKCa.
These are the differences of Ds RNA adjuvants and their finder in Table 1. It indicates that PICKCa\PIKA and Pamica specific the latter are more beneficial to patients because they are much safer and more effective than PIC, PICLC and PIC12U.
2.2. Control of Pamica
Pamica must meet the National Standard of PICKCa injection WS1-XG-050- 2000 from China Food and Drug Administration (CFDA) which is same as US FDA. The details are listed as following.
The conclusion in Table 2 was that Pamica met the Standard WS1-XG-050- 2000 of CFDA.
Table 1. Difference of DS RNA adjuvants  .
Table 2. National Standard of China FDA PICKCa injection WS1-XG-050-2000  .
3. Salvage Therapeutic Results to Late Stage Cancer with Pamica
3.1. Selection of Cancer Types
Table 3 showed that Pamica could treat many kinds of cancers including Carcinoma of salivary gland, Laryngocarcinoma, Esophaguus cancer, Liver cancer, Lung cancer, Coloretal cancer. In fact, pamica has no selection to trea cancers, Perhaps it associated with action mechanism of Pamica.
3.2. Selection of Cancer Patients
The patients received Pamica treatment were unresponsive to standard treatment. Patients were selected regardless of the type of tumor and performance status (ECOG above 5 or ECOG > 20), that is loss of self-care ability and in need of actively support treatment. All patients were informed and had given their consents to participate. The treatment was given free of charge.
3.3. Method of Application
Pamica is a non-antibiotics and non-cytotoxic dsRNA product. 2 mg/every two days, im or mist spray.
3.4. Clinical Effects
The patients were administered the drug by injection or nasal spray for 2 - 9 months. No side effects were observed other than a few cases of local pain in injection. Details are tabulated in the Table 3.
Table 3. Salvage therapeutic results to terminal cancer patients with Pamica.
These cases (Table 3) preliminarily indicated: 1) Satisfactory safety in cancer treatments. Pamica had no side effect excepting a few cases local pain near injection site. 2) Efficacy: Pamica appeared to be able to markedly improve patients’ appetite, physical strength, and state of mind, which also extended patients’ life for months and counting.
4. The Basic Research of Pamica
Pamica and PICKCa are ligands of pattern recognition receptors of TLR3, MDA5 and RIG-1. PICKCa vaccines can activate innate pathways in vivo to produce cytokines including IFN-α, IFN-β, IFN-γ, IL-2, IL-12p40, IL-6, TNF-α, promote macrophage function, stimulate antigen-presenting cells to produce co-stimulators of CD40, CD80, CD86, activate cell-mediated immunity and humoral immunity. Due to PICKCa adjuvant enhancing productions of IFN, IL-2, IL-12, the adjuvant may make prophylactic vaccines from main humoral immunity to possess strong cell-mediated immunity as therapeutic vaccines. In three independent experiments of post-explosure immunizations of mice and beagle dogs, PICKCa rabies vaccine was much better than commercial adjuvant-free rabies vaccines, the protective rate was 70% - 100% and 20% - 30% respectively, and the statistical analysis were significantly different (P < 0.05 - 0.001). PICKCa rabies vaccine and PICKCa hepatitis B vaccine had succeeded in phase II clinical trial and phase I trial in Singapore. Also PICKCa and its vaccines have cooperated with US including The Scrioos Intitute to AIDS, MRIID to Ebola, AERAS to tuberculosis and US FDA has approved PICKCa hepatitis B vaccine as anti-liver cancer orphan drug  -  .
Pamica is the second generation non-cytotoxic product of PICKCa. The difference between Pamica and PICKCa is that Pamica substitues non-antibiotic amino compounds for kanamycin in PICKCa. Pamica contains more amino groups which bond to the phosphate group in PIC making the double-strand more stable and not to be hydrolyzed as easily, therefore Pamica is more effective than PICKCa. In addition, without kanamycin which could cause hearing loss, Pamica is also safer than PICKCa  .
From the mechanism, it is an analog of PICKCa. Pamica (PICNH2Ca2) is effective cancer immunotherapy drug which significantly improves systemic immunity of Late Stage Cancer Patients including innate and acquired immunity also including CMI, BMI, CD8+, CD4+ and memory immunity and so on. That may be a key role to improve life quality and prolonged survival of terminal cancer patients although it is not to kill cancer cells directly.
Open question. However crude these clinical results may be, we found the findings exciting nonetheless. These tests were conducted without being monitored by hospital. They lacked the testing indexes in diagnosis and treatment. But it still showed promise that we may be at the doorstep of an effective treatment for late stage cancer.
In the future, first step should be expanding clinical trial of Pamica and be sure its safety and efficacy and then to extend it to first-line treatment or combination therapy with it to cancer patient. Although Pamica is much cheaper than mono-antibodies treated cancer, it is important for treating cancer patients.
We are publishing these crude results in the hope of cooperating with the proper authorities, companies, and hospitals to bring benefit to patients at the earliest opportunity.
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