CimaVax-EGF
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CimaVax-EGF is a vaccine used to treat cancer, specifically
non-small-cell lung carcinoma Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...
(NSCLC). CIMAvax-EGF is composed of recombinant human epidermal growth factor (EGF) conjugated to a protein carrier. The vaccine was developed by the Center of Molecular Immunology,
Havana, Cuba Havana (; ) is the capital and largest city of Cuba. The heart of La Habana Province, Havana is the country's main port and commercial center.Serbia , image_flag = Flag of Serbia.svg , national_motto = , image_coat = Coat of arms of Serbia.svg , national_anthem = () , image_map = , map_caption = Location of Serbia (gree ...
's Institute of Virology, Vaccines and Sera (AKA Torlak Institute) signed a memorandum for use in 30 patients as part of a study. CimaVax is relatively cheap to produce and store, and has low toxicity. It costs approximately USD $1 per shot to manufacture. Side effects of the vaccine appear to be mild, and include chills, fever, and feeling sick.


Mechanism

CimaVax is an active
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
with which patients are immunized with epidermal growth factor (EGF), thus raising
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
targeting EGF itself. The EGF is chemically linked to the '' Neisseria meningitidis'' outer protein P64k for immunogenicity; Montanide ISA 51 is used as an
adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Anal ...
to potentiate the immune response. The
epidermal growth factor receptor The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor (biochemistry), receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligand (biochemistry ...
(EGFR) is hijacked by many types of cancer, including cancers of the lung, colon, kidney, and head and neck. By raising antibodies against EGF, which is EGFR's major
ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
, the concentrations of EGF in the blood are reduced. Thus CimaVax does not target the cancer cells directly, but is expected to work against these cancers by denying the cancers the growth stimulus they require. For this reason, the Roswell Park Comprehensive Cancer Center group thinks that it may prove most useful as a ''preventive'' vaccine rather than as a cancer therapy ''per se''.


Research


Cuba

Early trials showed a trend towards improved survival among vaccinated test subjects. A direct correlation between the level of antibodies that a vaccinated patient raises against EGF and survival has been observed in several trials, and in one of the largest trials there was also an age-dependence, with only subjects under the age of 60 benefiting in terms of survival. More antibodies are raised when the vaccine is formulated with Montanide ISA 51 rather than aluminum hydroxide as an adjuvant, and when patients receive a low dose of cyclophosphamide three days before vaccine administration. Cyclophosphamide is thought to temporarily block the body's natural
immune tolerance Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specif ...
to EGF, thereby increasing antibody titers. Researchers caution that the early results to date have been in relatively small, early-stage trials with patients that were carefully selected based on predefined inclusion and exclusion criteria, and given specialized oncology care; they may therefore not be representative of most patients who might benefit from the vaccine. It has been urged that CimaVax be tested in patients with earlier-stage NSCLC cancer and in patients who are not candidates for
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
, and that research be conducted to determine which subgroups of NSCLC patients do and don't respond to the vaccine. It has been suggested that CimaVax may also be effective in other types of cancer that are dependent on EGF/EGFR, including many cases of
prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...
. In Cuba, CimaVax-EGF has completed a phase IV clinical trial for NSCLC in 2017. It is approved as a "maintenance treatment for patients with stage IIIB/IV NSCLC".


International

The United States embargo against Cuba forbids US citizens from seeking medical treatment in Cuba. However, some cancer patients from the US have defied the embargo and travelled to Cuba for treatment with CimaVax. Trials are being organized in the United States, the European Union, Japan, and Serbia. In late October 2016, the
United States Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
authorized Roswell Park Comprehensive Cancer Center to conduct a PhaseI/II clinical trial of CimaVAX in patients with non-small cell lung cancer. By the middle of the following month, nearly 200 people had volunteered to be subjects in the trial. In September 2018, Principal Investigator Grace Dy shared the initial results of the first Roswell Park trial. They found that the combination of CIMAvax with the PD-1 inhibitor
checkpoint inhibitor Checkpoint inhibitor therapy is a form of Treatment of cancer, cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some ca ...
nivolumab was safe and well tolerated in 13 people with advanced
non-small cell lung cancer Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...
(NSCLC) when administered at the doses normally recommended for each agent individually. Notably, they observed durable responses to the combination treatment in patients who were unlikely to benefit from nivolumab alone due to low tumor levels of PD-L1, suggesting that the combination may work better than either agent individually. The final results of this early trial were released in March 2019. The results were in line with the September 2018 report, with the additional finding that patients receiving combination therapy in this trial were more likely to develop robust early antibody responses to CIMAvax as compared with what had been observed in earlier studies with CIMAvax alone. An ongoing Phase II clinical trial (
clinicaltrials.gov ClinicalTrials.gov is a clinical trials registry, registry of clinical trials. It is run by the United States National Library of Medicine (NLM) at the National Institutes of Health, and holds registrations from over 444,000 trials from 221 cou ...
identifier NCT02955290) has been expanded to include patients with advanced, recurrent head and neck squamous-cell carcinoma, as well as patients with advanced NSCLC but with high PD-L1 levels, who will be treated with pembrolizumab in combination with CIMAvax instead of nivolumab. As of 2023, accrual for this phase II trial is ongoing.


See also

* Racotumomab


References

{{Reflist Cancer vaccines Healthcare in Cuba Cuban inventions