(Disclaimer- I am an engineer and not a microbiologist/doctor)

Mutations and wrong copying of genome happens all the time in the body and some enzyme has the job of correcting the mutated genes so it doesn’t get into the system. Level 2 defence is T cells killing it as identified as foreign body.

Thing that baffles me is that I see most work happening to eliminate tumor. To me it sounds a tough problem given the permutation and combination of mutation— roughly few trillions.

But I was curious if there is working happening on L1 defence — fixing the enzyme that fixes the wrong copy paste mechanism. Or making the enzyme get more efficient and powerful. Is that line of thought even valid?

This sounds like world changing news. Can anyone with domain expertise explain the catch, if any?

Also agree that using a PD-L1 mab feels like it’s for show especially considering the cancer model they’re using (Colon-26) was shown to be substantially less responsive to PD-L1 inhibitors…

Not the world’s best paper imo

"Tumor-Specific Accumulation Mechanism

E. americana selectively accumulates in tumor tissues with zero colonization in normal organs. This remarkable tumor specificity arises from multiple synergistic mechanisms:

Hypoxic Environment: The characteristic hypoxia of tumor tissues promotes anaerobic bacterial proliferation

Immunosuppressive Environment: CD47 protein expressed by cancer cells creates local immunosuppression, forming a permissive niche for bacterial survival

Abnormal Vascular Structure: Tumor vessels are leaky, facilitating bacterial extravasation

Metabolic Abnormalities: Tumor-specific metabolites support selective bacterial growth

Excellent Safety Profile

Comprehensive safety evaluation revealed that E. americana demonstrates:

Rapid blood clearance (half-life ~1.2 hours, completely undetectable at 24 hours)

Zero bacterial colonization in normal organs including liver, spleen, lung, kidney, and heart

Only transient mild inflammatory responses, normalizing within 72 hours

No chronic toxicity during 60-day extended observation"

Well, I guess Leukemia has been somewhat cured I heard, so that's pretty huge. When I was a kid it was a death sentence IIRC.

Several things trigger my bullshit meter. Quote:

"This dramatically surpasses the therapeutic efficacy of current standard treatments, including immune checkpoint inhibitors (anti-PD-L1 antibody) and liposomal doxorubicin (chemotherapy agents)"

PD-L1 monoclonal antibodies are only effective against cancers that are, you guessed it, PD-L1 positive. At high percentages, ranging from 1 to 50%. Are these authors even familiar with the state of the art when it comes to cancer medications? Mouse tumors do not equate to people tumors. Many tumor types are not PD-l1 positive.

Doxy is an ancient SOC chemo.

This is a nothing burger.

Give me phase II/III clinical trials, and then let me know what their PFS/OS was after 5 years. and what the medians were at 3- and 5-years. Also, ORR and CR and needed.

CAR-T is ahead of the game, and will be the ultimate winner here as it grows to scale.