Lost Soviet Research Reveals The Link Between Pregnancy and Cancer?

Leveraging clinically-evidenced placental based therapies to train the body to fight cancer

What You need To Know

Valentine Ivanovich Govallo, considered by many to be the founder of Immunotherapy in Russia, pioneered placental based therapies that train your immune system to attack and kill cancer
In the 1970s, he treated over 35 patients with various solid tumor carcinomas (lung cancer, breast cacner, colorectal, melanoma) and reported a 65% 10 year survival rate. Unfortunately at the time a detailed understanding of how his therapy works had yet to be demonstrated.
Today, several independent research publications have validated that there are many antigens found in the placenta that are shared with almost all solid tumor carcinomas.
Batu Biologics has developed a second generation of the original Govallo vaccine, and researchers are looking to reproduce Govallo’s original results.
Batu Biologics lead product, ValloVax, is a placentally derived cellular therapy that trains the immune system to attack and kill the vasculature of solid tumors. This therapy is currently exclusively available to patients at the CHIPSA Hospital, and we would like to evaluate whether you are an ideal candidate for therapy.

Introduction

The potential of utilizing the body’s own natural defenses to seek and kill cancer has fascinated researchers for over one hundred years. Rapid technical innovations in the field of genomics, molecular, and cellular biology are paving the way for a new era of effective immunotherapies for the treatment of cancer.

It has long been understood that certain cancers express a number of identifying molecular features or antigens on their cell surface that can be recognized by the body’s immune cells. The problem is that cancer takes several steps toward evading or escaping detection from the immune system. One of the primary methods that the tumor utilizes to escape destruction from the immune system is by promoting a locally immunosuppressive environment that prevents your body’s immune cells from functioning properly. Essentially, the tumor is able to create a tolergenic environment that tells your immune system to “leave me alone!”.

The concept of using a therapeutic intervention to create or break immunological tolerance in the body has been one of the key pillars of the booming immunotherapy industry. Many researchers have been working to modulate immunological tolerance in the body through novel vaccine therapies, the goal of which is to stimulate an immune response against antigens specific to cancer.

Dr. Valentine Ivanovich Govallo’s Immunotherapeutic Approach to Treating Cancer

In this article we would like to review the work of Dr. Valentine Govallo, a clinical and tumor immunologist from Moscow who is considered by many to be the founder of Immunotherapy in Russia. Dr. Govallo, throughout his lifetime, accumulated over 40 years of experience in clinical immunology, was the author of 294 scientific papers and 19 scientific books. The International Biographical Committee in Cambridge also awarded Govallo with “Man of the Year 2000” including him with 2000 other outstanding scientists who made an impact during the 20^th century. Most recently, in 1993, Govallo published his book “Immunology of Pregnancy and Cancer” with the publishing house Nova Science which documented his most notable scientific discoveries.

Govallo’s research culminated in the development of a novel cellular based cancer immunotherapy he called “immunoplacental therapy (IPT)”, which consisted of chorionic villi extractions from a human placenta following a full term delivery. Govallo was initially obsessed during the 1970s with the remarkable similarities in endocrine profiles between placental and cancer tissue.¹ Govallo viewed the placenta as a unique biological phenomenon that can be used to study cancer several shared features with established tumors:

The fetus with foreign paternal antigens behaves similar to a tumor and is not rejected by the mother’s immune system. Tolerance is created to new antigens that the immune system should target and kill.
The placenta causes immunosuppression locally, supporting this tolergenic environment.
There exists in the placenta a hyper-proliferation of blood vessels not normally found in the body except within cancer.

Govallo’s original theory was that placental antigens could be used to stimulate an immune response against the cancer itself. To further pursue his original theory, Govallo conducted two clinical studies in humans to evaluate his immunotherapeutic methods of treating cancer.

His first study was conducted in 1973, where he developed an integrative protocol to treat cancer that consisted of methods of immune stimulation and targeted vaccine therapy. He stimulated the immune system through passive lymphocyte transfer, stimulation, and co-administration of adjuvant BCG to drive an immune response. Govallo, also included in this protocol an autologous tumor cell vaccine and an embryonic cell (non-placental tissue) injection. The study consisted of 66 patients with a range of malignant solid tumor carcinomas. The three, five, and ten year survival rates for this therapy were 12%, 6%, and 2% respectively across all cancer indications.³

Govallo was unimpressed with the results of his original study and conducted a second clinical trial in 1975 with a new approach to stimulating the immune system. In his second study, Govallo took placental extracts from full term deliveries and used them to develop his novel cancer vaccine therapy dubbed the “Immunoplacental Therapy”. This clinical study focused on cancers of the breast (18 patients), lung (7 patients), malignant hemangiopericytoma (10 patients), synovial sarcoma (10 patients), and colorectal cancer (10 patients). The aggregated three, five, and 10 year survival rates for this study were 88%, 77%, and 65% respectively.³ Govallo’s results were fascinating, however he still did not have a defined molecular basis for the vaccines observed effectiveness.

Govallo’s Frustration

To Govallo’s frustration, several groups have pirated his therapy without his permission, commercializing a placental based immune therapy named VG-1000. In recent interviews, Govallo claimed that many of these institutions were improperly following his original methodology. Regardless, Govallo’s initial research set the stage for many new scientists to further explore the link between pregnancy and cancer with the goal of developing less toxic therapies to replace the conventional medicine approach to treating solid tumors.

Interestingly enough, shortly after Govallo began his clinical studies in Russia, another independent group of scientist in Canada replicated his work in animal models using placental tissue as a vaccine therapy, and they published their work in the British Journal of Cancer in 1978.² Similarly, this group hypothesized that the vaccine could induce a heightened state of immunity against antigens shared with the placenta and cancer. They identified a subset of antigens that could potentially be shared with the placenta and cancer in their work.

Within the past 10 years, advancements in molecular biology, and genomics have unveiled a plethora of antigens that are shared between the placenta and several histologically distinct tumors. The following table outlines some of the antigens common to both cancer and placental tissue:

Table 1	Antigens Shared Between Specific Cancers and Placental Tissue
Melanoma	Angiogenesis antigens: EGFR³⁰, TEM-1³¹, Endoglin³² Tumor associated antigens: Cancer testes antigens (MAGE, NY-ESO-1, SSX antigen)^4,5, glypican-3²⁷, survivin⁹
Colon	Angiogenesis antigens: EGFR³³, Endoglin, VEGF³⁴, TEM-1³⁴ Tumor associated antigens: CEA, CSA, SP1⁶, PLAP, HCG, HPL, AFP, FE, TF⁷, 5T4⁸, survivin⁹, FasL³⁷
Ovarian	Angiogenesis antigens: Endoglin³⁶ VEGF-R1, VEGF-R2⁴⁰, TEM-1³⁴ Tumor associated antigens: PLAP, HCG, CEA, AFP, Bjorkland’s antigen¹⁰, CTA (SCP-1)¹¹, LK-26¹², CA-125^13,14, FasL³⁷
Breast	Angiogenesis antigens: TEM-1³⁵, VEGF-R1, VEGF-R2, Endoglin³⁹ Tumor associated antigens: PLF¹⁵, PLAP¹⁶, CA-125, CEA¹⁴, CD46¹⁷, FasL³⁷
Lung	Angiogenesis antigens: VEGF-R1, VEGF-R2⁴², EGFR, TEM-1³⁸, Endoglin⁴² Tumor associated antigens: PLAP¹⁶, Cancer Testes Antigens (MAGE, SP1)^18,19, Ki-1 (CD30) antigen²⁴, CEA, HCG²¹
Prostate	Angiogenesis antigens: VEGF, FGF Tumor associated antigens: Prostate stem cell antigen (PSCA)²⁰, PSA, HCG²¹, Cancer Testis Antigen (PAGE)²², FasL³⁷
Testicular	Angiogenesis antigens:VEGF, EGFR Tumor associated antigens: PLAP²³, Ki-1 (CD30) antigen²⁴
Gastric	Angiogenesis antigens:TEM-1³⁸ Tumor associated antigens: 5T4⁸, PLAP¹⁶
Sarcoma	Tumor associated antigens: Cancer Testis Antigen (XAGE)²⁵, SSX²⁶
Lymphoma	Tumor associated antigens: Ki-1 (CD30) antigen²⁴
Hepatocellular	Angiogenesis antigens: VEGF-R1, VEGF-R2, EGFR, TEM-1³⁸, Endoglin Tumor associated antigens: Glypican-3²⁷ CTA²⁸

Note. Reprinted [adapted] from “Immunoplacental therapy, a potential multi-epitope cancer vaccine.” By Harandi A., 2006, Med Hypotheses, 66(6):1182-7.

Batu Biologics and A Second Generation Govallo Vaccine: ValloVax

San Diego-based biotechnology firm, Batu Biologics, is not letting Govallo’s original research sit by the wayside. Batu Biologics is seeking to continue Govallo’s original research to identify the active components found in the placenta that are able to confer anti-tumor immunity in patients, and commercialize this new therapy with the US FDA.

Batu Biologics focuses on the similarities between blood vessel formation in the placenta and in cancer. The placental endothelium expresses a large number of angiogenic proteins that are also found expressed on the tumor associated vasculature.²⁹ Batu Biologics lead product is comprised of placentally derived endothelial cells that are grown under conditions that mimic the tumor microenvironment, resulting in a final cellular product that has a similar phenotype to the blood vessels of cancer. Batu Biologics recently published data demonstrating that mice had an antibody and cellular immune response against VEGF-R1, VEGF-R2, Endoglin, TEM-1, EGFR,²⁹ which are all known to play a role in angiogenesis for many types of cancer.

The goal of their therapy is to stimulate your body to kill the ValloVax cells, which will result in a cross reaction against the vasculature of solid tumors, which shares many of the immunological targets found on the original immunization. The Company had demonstrated proof of concept in multiple animal models for melanoma, breast cancer, lung cancer, colorectal cancer, and glioblastoma.²⁹ ValloVax has recently completed an 8 patient first-in-human feasibility study in which safety and immunological response was demonstrated. The Company has filed an Investigational New Drug application with the US Food and Drug Administration and anticipates approval to move forward with further clinical studies in the US in early 2018.

“The ValloVax immune therapy was designed to stimulate an immune response against the tumor vasculature to induce collateral damage to the tumor itself by cutting off the blood supply. However recent research illuminating the many shared antigens between the placenta and cancer highlight the possibility that ValloVax may induce an immune response against the cancer itself. We see that there are many potential clinical applications for a universal cancer vaccine that stimulates a response against a wide range of tumor epitopes, thus decreasing the likelihood that the tumor will be able to escape therapeutic intervention,” stated Samuel C. Wagner, President and CEO of Batu Biologics.

Currently, ValloVax, is available for qualifying patients as part of an Investigator Initiated Clinical Study in collaboration with the CHIPSA hospital who has exclusive access to the immune therapy within Mexico. Researchers are excited about the potential of continueing Govallo’s promising work and eventually reproducing his results in a double-blinded placebo controlled clinical setting.

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