Browsed by
Month: February 2025

TIL:  Tumor Infiltrating Lymphocyte Therapy 

TIL:  Tumor Infiltrating Lymphocyte Therapy 

TIL is a recently FDA approved therapy for treating certain types of metastatic cancer.  It has been referred to as a “living drug” as it is made up of the individual patients T lymphocytes.  It does so by taking cancer-targeting T cells from the patient’s own tumor and then growing them into billions more of the same cells in the lab and then re-infusing them into the patient.   This massive influx of warrior T cells can destroy the tumor whereas the previous small number of T cells were just holding it at bay.  

The initial FDA approval is for metastatic melanoma, but it’s used for other solid tumors such as breast, pancreas and colon cancers.   

TIL is not the first use of immune cells to fight cancer.  CAR T-Cell therapy is another FDA approved method to fight certain “liquid” cancers, primarily leukemia, lymphoma, and multiple myeloma.  So far it has not proven effective for solid cancers.  CAR T-Cell therapy is so named because it involves making a chimeric antigen receptor (CAR) on T-cells.  It uses genetic engineering to modify the patient’s own T-cells so they can recognize (and then destroy) a specific cancer cell signal (antigen).  CAR-T therapy has helped and cured thousands of patients but one drawback of its use is that it is tricky to find a molecular signal (antigen) that is totally unique to the cancer.  Since healthy cells may also share this molecular signal, they can sometimes be damaged by the chimeric T-cells.  TIL on the other hand doesn’t modify the innate targeting system of the T-cells it simply uses a normal immune cytokine IL-2 (interleukin-2) to boost cell growth.  As it turns out one “target” that the TIL cells seem to pick out is the mutated protein that would otherwise control healthy cell growth.  Once this protein undergoes a Jekyll-Hyde transformation it allows uncontrolled cell growth otherwise known as cancer.   

Leukocyte Activation and COVID-19 Vaccine Reactions 

Leukocyte Activation and COVID-19 Vaccine Reactions 

Luckily severe allergic reactions (anaphylaxis) to COVID-19 vaccines have been rare, averaging about 8 events per million vaccines.  However, since the Corona virus continues to circulate there will be an ongoing need for vaccination.  Based on current research it seems that most of these adverse events are reactions to polyethylene glycol (PEG).  However, attempts using traditional allergy testing techniques which look for IgE mediated sensitivity have led to poor discriminatory value in people who have had allergic reactions and poor predictive value when used to try and prophylactically identify individuals at high risk for allergic reactions.  This frustration has led to research to identify a more reliable test.  Georgetown University has used a research test called leukocyte activation with surprisingly good results.  The test is done by adding PEG to a sample of the patients’ blood and then analyzing it to see if the leukocytes (white blood cells) become activated.   

So far this is just a research tool but it could lead to a readily available testing mechanism, much as the home Covid test swab has become.   

Dear Dr. K – 

Dear Dr. K – 

I read that there might be a new asthma controlling shot that is given just every six months.  Is that true?  

Yes, it is true.  Researchers at Oxford University have just completed two phase 3A randomized placebo control trials that look very promising.  The new drug is depemokimab and it is a monoclonal antibody (note the “mab” at the end of its name) that binds to Interleukin 5.  In fact, it has an incredibly strong binding affinity for Interleukin 5 which allows for just twice a year dosing.  Interleukin 5 is an inflammation causing cytokine that is responsible for the growth, recruitment, activation and survival of eosinophils.  Eosinophils are white blood cells that are the cause of most asthma.  Make the eosinophils go away and you make the asthma go away.    

There are other currently available drugs that are also very effective in controlling asthma that target Interleukin 5.  But they require more frequent dosing.  Also, all of these medications are only indicated in severe asthma that is not adequately controlled with inhaled steroids.   

In the two Oxford trials, depemokimab was very effective in improving asthmatic symptoms and in reducing exacerbations.  The side effect profile was similar to that of the placebo control.  Still, it won’t be available until it meets FDA approval.   

Processed Milk and EOE 

Processed Milk and EOE 

There is mounting evidence that processed milk is the primary cause for the newly developing epidemic of eosinophilic esophagitis (EOE).  The rise of EOE began after the widespread consumption of ultra heat treatment (UHT) pasteurization and micro fluidization homogenization of our milk in the early 1990’s.   

Louis Pasteur recommended heating milk to 72° C for 15 seconds.  UHT heats milk to 140° C.  Homogenization is a process to reduce the fat droplet size so that milk doesn’t separate in the container.  This highly processed milk makes it very pleasing to the eye (uniformly white) and gives it a long shelf life.  In fact, it actually does not require refrigeration.  But in the American market consumers’ unease about drinking non-refrigerated milk has led to most milk being sold cold.  Prior to this ultra processing the cold was necessary to preserve the milk.   

Unfortunately, this ultra-processing (UP) markedly alters both the fat and the protein in milk in a way that creates inflammation in the esophagus.  Also, there are small amounts of detergent residue in milk.  Very strong detergents are used to clean the processing equipment in order to prevent biofilms.  This detergent residue causes a chemical injury that disrupts the normal intact cellular barrier in the esophagus.  These micro-fissures in the esophageal membrane allow the penetration of fat-protein nanoparticles which in turn instigate the incursion of the eosinophils.  Prior to UP there was no detergent residue in milk and the milk proteins/fats were large and did not infiltrate the esophageal lining. 

Finally, there is early evidence that strictly avoiding cow milk and its products (cheese, butter, yoghurt, ice cream) leads to healing of EOE.