Thread by @AdamJBrownMD

Cancer and mycobacterium Tuberculosis, both ancient foes of humans

How did we get to the point of fighting cancer WITH a form of mycobacterium?

and what does this have to do with Rheumatology?

let's investigate! 🧵

#meded #cancer #urology @LCalabreseDO @HRheuminations

Let's start with a little background on BCG vaccine

Calmette and Guerin (the C and G), worked on a vaccine to protect people from the scourge that was/is mycobacterium tuberculosis

how to do this?

Step 1

Isolate a similar bacterium off a cow (M. bovis)

thanks cow

Step 2

Run it over a funky concoction of potatoes, glycerin and cow bile (delicious!)

M. Bovis lost virulence after multiple passages over cultures

(similar process done with rabies vaccine, so the Pasteur institute knew a thing or two about how to do this)

Now what?

1915 Give it to a cow, then expose cow to TB. cow does not get TB. Victory!

ready for humans? not yet

Keep running the M. Bovis (now called BCG) over cultures (231 times to be exact) now bacteria is super chill. doesn't want to hurt anyone.

1921 give BCG to a baby whose mother AND grandmother died of TB and was at high risk of infection

☑️ Baby did great. Did not develop TB

1924 the big test. 217 Parisian children vaccinated with BCG, ⬇️TB and no major side effects

Now BCG vaccine becomes a thing

Okay, great now we know about BCG vaccine.

What does this have to do with cancer?

It turns out, a link was made in 1929 by a pathologist at Johns Hopkins

Recognized patients who died of tuberculosis, for the most part, did NOT also have cancer.

Fast Forward to the 1950s, Lloyd Old (of TNF fame), showed mice infected with BCG has more resistance to transplantable tumors.

Also recognized it wasn't BCG attacking the cancer, BCG augmented the immune system, triggering macrophages against tumor cells

Immunotherapy!

1970s Led to a boom in injecting BCG into all sorts of cancers.

some reports showed it was helpful but the results weren't overwhelming and BCG was soon replaced with more effective therapies.

...except for bladder cancer

1976 Alvaro Morales, a Urologist in Canada gave intravesical BCG to treat superficial bladder cancer.

🔟 patients

Gave combo of 120 mg of BCG and 50 ml of saline via a urethral catheter

6⃣ weekly treatments.

no tumor recurrence in 7 patients

1990 after 2,500 cases pooled worldwide

FDA approves intravesical BCG for the treatment of superficial bladder tumors.

In summary:

BCG was developed from M. bovis as a vaccine against M. tuberculosis

Mice infected with BCG ⬆️ resistance to tumors

Found injecting BCG superficially triggers a massive immune response to fight off certain types of cancer

....what does this have to do with Rheumatology?

it turns out, this massive immune response to the BCG can also trigger a severe Reactive Arthritis type syndrome!

learn more take a listen

protect-us.mimecast.com/s/APRYC1wqKkH6…

Reference:

Herr HW, Morales A. History of bacillus Calmette-Guerin and bladder cancer: an immunotherapy success story. J Urol. 2008