How mRNA and DNA vaccines could soon treat cancers, HIV, autoimmune disorders and genetic diseases

The idea of using genetic material to produce an immune response has opened up a world of research and potential medical uses far out of reach of traditional vaccines. Deborah Fuller is a microbiologist at the University of Washington who has been studying genetic vaccines for more than 20 years. We spoke to her about the future of mRNA vaccines.

Below are excerpts from that conversation which have been edited for length and clarity.

This article is a repost which originally appeared on The Conversation
Deborah Fuller - January 6, 2022
Edited for content and readability - Images sourced from Pexels 

Our Takeaways:

  • Nucleic acid vaccines are based on the idea that DNA makes RNA and then RNA makes proteins.
  • These vaccines are effective at inducing a T cell response.
  • For cancer, the goal is to make your body better able to recognize the very specific neoantigens the cancer cell has produced and destroy it.
  • For autoimmune disorders, the vaccine would suppress the T Cells to keep the immune system from attacking myelin

How long have gene-based vaccines been in development?

This type of vaccine has been in the works for about 30 years. Nucleic acid vaccines are based on the idea that DNA makes RNA and then RNA makes proteins. For any given protein, once we know the genetic sequence or code, we can design an mRNA or DNA molecule that prompts a person’s cells to start making it.

When we first thought about this idea of putting a genetic code into somebody’s cells, we were studying both DNA and RNA. The mRNA vaccines did not work very well at first. They were unstable and they caused pretty strong immune responses that were not necessarily desirable. For a very long time DNA vaccines took the front seat, and the very first clinical trials were with a DNA vaccine.

But about seven or eight years ago, mRNA vaccines started to take the lead. Researchers solved a lot of the problems – notably the instability – and discovered new technologies to deliver mRNA into cells and ways of modifying the coding sequence to make the vaccines a lot more safe to use in humans.

Once those problems were solved, the technology was really poised to become a revolutionary tool for medicine.

What makes nucleic acid vaccines different from traditional vaccines?

Most vaccines induce antibody responses. Antibodies are the primary immune mechanism that blocks infections. As we began to study nucleic acid vaccines, we discovered that because these vaccines are expressed within our cells, they were also very effective at inducing a T cell response. This discovery really prompted additional thinking about how researchers could use nucleic acid vaccines not just for infectious diseases, but also for immunotherapy to treat cancers and chronic infectious diseases – like HIV, hepatitis B and herpes – as well as autoimmune disorders and even for gene therapy.

How can a vaccine treat cancers or chronic infectious diseases?

T cell responses are very important for identifying cells infected with chronic diseases and aberrant cancer cells. They also play a big role in eliminating these cells from the body.

When a cell becomes cancerous, it starts producing neoantigens. In normal cases, the immune system detects these neoantigens, recognizes that something’s wrong with the cell and eliminates it. The reason some people get tumors is that their immune system isn’t quite capable of eliminating the tumor cells, so the cells propagate.

With an mRNA or DNA vaccine, the goal is to make your body better able to recognize the very specific neoantigens the cancer cell has produced. If your immune system can recognize and see those better, it will attack the cancer cells and eliminate them from the body.

This same strategy can be applied to the elimination of chronic infections like HIV, hepatitis B and herpes. These viruses infect the human body and stay in the body forever unless the immune system eliminates them. Similar to the way nucleic acid vaccines can train the immune system to eliminate cancer cells, they can be used to train our immune cells to recognize and eliminate chronically infected cells.

What is the status of these vaccines?

Some of the very first clinical trials of nucleic acid vaccines happened in the 1990s and were for cancer, particularly for melanoma.

Today, there are a number of ongoing mRNA clinical trials for the treatment of melanoma, prostate cancer, ovarian cancer, breast cancer, leukemia, glioblastoma and others, and there have been some promising outcomes. Moderna recently announced promising results with its phase 1 trial using mRNA to treat solid tumors and lymphoma

There are also a lot of ongoing trials looking at cancer DNA vaccines, because DNA vaccines are particularly effective in inducing T cell responses. A company called Inovio recently demonstrated a significant impact on cervical cancer caused by human papilloma virus in women using a DNA vaccine.

Can nucleic acid vaccines treat autoimmune disorders?

Autoimmune disorders occur when a person’s immune cells are actually attacking a part of the person’s own body. An example of this is multiple sclerosis. If you have multiple sclerosis, your own immune cells are attacking myelin, a protein that coats the nerve cells in your muscles.

The way to eliminate an autoimmune disorder is to modulate your immune cells to prevent them from attacking your own proteins. In contrast to vaccines, whose goal is to stimulate the immune system to better recognize something, treatment for autoimmune diseases seeks to dampen the immune system so that it stops attacking something it shouldn’t. Recently, researchers created an mRNA vaccine encoding a myelin protein with slightly tweaked genetic instructions to prevent it from stimulating immune responses. Instead of activating normal T cells that increase immune responses, the vaccine caused the body to produce T regulatory cells that specifically suppressed only the T cells that were attacking myelin.

Any other applications of the new vaccine technology?

The last application is actually one of the very first things that researchers thought about using DNA and mRNA vaccines for: gene therapy. Some people are born missing certain genes. The goal with gene therapy is to supply cells with the missing instructions they need to produce an important protein.

A great example of this is cystic fibrosis, a genetic disease caused by mutations in a single gene. Using DNA or an mRNA vaccine, researchers are investigating the feasibility of essentially replacing the missing gene and allowing someone’s body to transiently produce the missing protein. Once the protein is present, the symptoms could disappear, at least temporarily. The mRNA would not persist very long in the human body, nor would it integrate into people’s genomes or change the genome in any way. So additional doses would be needed as the effect wore off.

Research has shown that this concept is feasible, but it still needs some work.

What Are the Five Warning Signs of Testicular Cancer?

What Are the Five Warning Signs of Testicular Cancer?

Medical Author: Rohini Radhakrishnan, ENT, Head and Neck Surgeon Medical Editor: Dr. Pallavi Suyog Uttekar, MD

This article is a repost which originally appeared on MedicineNet

Edited for content

What is testicular cancer?

Testicular cancer warning signs include a testicular lump, back pain, swelling, and infection.

Testicular cancer arises from the testes (a part of the male reproductive system). The testicles are responsible for the production of male sex hormones and sperm for reproduction. They are located within the scrotum, a loose bag of skin below the penis. Testicular cancer is the most common type of cancer occurring in males in the US between the ages of 15 and 35.

Testicular cancer can be aggressive and grow and spread rapidly. However, this cancer is highly treatable even after it spreads. Hence, the prognosis for men with testicular cancer is good. Studies have shown that the risk of dying from testicular cancer is about 1 in 5,000.

How is testicular cancer treated?

The treatment may involve one or a combination of multiple treatment modalities, which depends on the extent of the disease.

The treatment options include

  • Surgery
    • Orchiectomy: Removal of the testicle. A prosthetic can be placed in the sac.
    • Testes-sparing surgery: The tumor is carefully removed and the healthy part of the testis is left behind. This is ideal for patients with small tumors or benign/noncancerous tumors.
    • Retroperitoneal lymph node dissection: Surgical removal of the lymph nodes to which cancer commonly spreads.
  • Radiation therapy: This targets and kills cancer cells and shrinks tumors using radiation.
  • Chemotherapy: The tumor cells are killed with cancer medication.
  • Targeted therapy: This treatment uses medications that target tumor-specific proteins that the cancer cells display. This is the most specific therapy for cancer and known for minimal side effects.
  • Stem cell therapy may be a treatment option in some cases. However, stem cell therapy is still in the experimental stages in most countries.

What causes testicular cancer?

The exact cause of testicular cancer is unknown. Some factors increase the risk of testicular cancer, including

  • Undescended testes (cryptorchidism) are a risk factor for the development of testicular cancer. Surgical correction of undescended testes before puberty reduces the risk of testicular cancer.
  • Age: Testicular cancer usually occurs in males between the agesof 20 to 35.
  • Race: Testicular cancer is more common in Caucasian men than in those of other races.
  • Genetic conditions like Klinefelter syndrome cause abnormal development of the testes.
  • Family history of cancer.
  • Human immunodeficiency virus (HIV) infection.

What are the warning signs of testicular cancer?

The initial signs and symptoms of testicular cancer include

  • A painless lump in the testicle.
  • Dull aching in the scrotum or the groin.
  • Varicocele (swollen blood vessels) appearing as enlarged, dark blue veins.
  • Hydrocele (fluid around the testicle) causing swelling.
  • Twisting of the testicle (torsion) may be the presenting symptom. On further investigation, the mass may be discovered.
  • The affected testicle feels firmer and harder than the other.
  • Formation of blood clots in blood vessels which can reach the lungs causing chest pain and breathlessness.
  • Back pain.
  • Infection of the testicle can occur causing pain.

What are the types of testicular cancer?

Most testicular cancers are germ cell (cells that produce sperm) tumors. There are two main types of testicular cancer, seminomas and nonseminomas.

  • Seminomas grow and spread slowly. There are two subtypes
    • Classical seminoma: This is the most common type and it usually occurs in men between the ages of 25 to 45.
    • Spermatocytic seminoma: This commonly occurs in older men and it usually does not spread.
  • Nonseminomas grow and spread more quickly. They usually consist of multiple types of cancer cells, including
  • Embryonal carcinoma: This cancer contains cells that look like embryonic cells under a microscope.
  • Yolk sac carcinoma: This cancer contains cells that look like the sac that surrounds an embryo. This cancer usually occurs in children.
  • Choriocarcinoma: This cancer is usually rare and spreads to the rest of the body quickly.
  • Teratoma: This is a rare tumor that contains other tissues and organs, including teeth and hair.

How is testicular cancer diagnosed?

  • Self-examination can help in early diagnosis and treatment. The affected testis is enlarged, firm and usually painless.
  • The physician orders testicular sonography and Doppler ultrasound to reveal the tumor. The physician performs a complete physical assessment.
  • A testicular biopsy confirms the diagnosis. It is a minimally invasive procedure that involves obtaining a small sample of the testicle.
  • Testicular magnetic resonance imaging (MRI) may reveal the extent of the tumor.
  • Lymphangiography may be performed to assess the local spread of the tumor to the lymph nodes of the groin.

June 1 kicked off National Men’s Health Month

June 1 kicked off National Men’s Health Month

This article is a repost which originally appeared on The Pioneer

Father’s Day is quickly approaching, and now is the perfect time to encourage the men in your life to take care of themselves by eating right, exercising and seeking regular medical care so they may live long and healthy lives.

The month of June is National Men’s Health Month and District Health Department No. 10 urges all boys and men to stay healthy by seeking regular medical checkups.

“The purpose of Men’s Health Month is to increase awareness of preventable health problems and encourage early detection and treatment of diseases in boys and men,” DHD No. 10 health officer Kevin Hughes said.

Men’s health is not just a ‘man’s issue’ it is a family issue. Men’s health can impact everyone around them: wives, mothers, daughters, and sisters. So, what can men do to be healthier?

• Eat healthy: Add more fruits and vegetable into your diet and try to limit eating foods that are high in calories, sugar, salt and fat.

• Get moving: Make a personal goal to reach 2 ½ hours of physical activity per week. Participating in activities you enjoy will help you to stay motivated.

• Quit tobacco: Tobacco smoking is the number one preventable cause of death in the U.S. and the primary cause of COPD and lung cancer.

• Make prevention a priority: Schedule yearly checkups and regular health screenings with your doctor or local health department. Monthly testicular self-exams are important for the early detection of testicular cancer

• Set an example: consistently pull the above healthy habits together and be a role model for those who may be watching you.

• Get tested: June 27 is National HIV Testing Day and everyone between the ages of 13 and 64 should get tested for HIV at least once as part of their routine health care. Those who are at a higher risk for HIV should be tested more often. For free HIV testing, contact your local Health Department.

DHD No. 10 offers several services for men including HIV testing, Sexually Transmitted Disease (STD) testing, treatment and prevention, sexual health exams, tobacco cessation programs, diabetes prevention programs, immunizations, and more.

To learn more about the programs offered for men or to schedule a service, call 888-217-3904.