anyone here with Kras T53 mutation

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Jackar0e
Posts: 10
Joined: Fri Feb 10, 2017 8:55 pm
Facebook Username: Amy Cremisio
Location: Waterford, NY

anyone here with Kras T53 mutation

Postby Jackar0e » Fri Jun 08, 2018 6:49 am

Hello,

I had the Hai pump installed in February. Still tumor is growing. I wasd told nasty cancer was Kras+T54 mutation. They want to try oxy and 5FU systemically and myocin and in the pump

I am thinking this is a shot in the dark. Any info??
44yrs old /Female
DX: Rectal Cancer
Tumor Location: If RC lower rectum,colon
Tumor type: carcinoma,
Tumor size 13mm

G1: Well differentiated
Stage : Stage IV
Mets: Liver
Baseline CEA value
Lymphovascular invasion : present


KRAS +

Chemotherapy XELOX, CAPEOX, FOLFOX,

NHMike
Posts: 1558
Joined: Fri Jul 21, 2017 3:43 am

Re: anyone here with Kras T53 mutation

Postby NHMike » Fri Jun 08, 2018 9:24 am

Gene mutations are often cited with the Gene and the individual mutation. I have KRAS G12D, so KRAS is the gene, 12 is the codon location, D indicates the kind of substitution and I don't recall what the first character means.

This is a good page to explore the known gene mutations and the individual mutations:

http://targetedcancercare.massgeneral.o ... /TP53.aspx

Image

Image
6/17: ER rectal bleeding; Colonoscopy
7/17: Stage 3B rectal. T3N1bM0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6, 5 x 5
7/17-9/17: Xeloda +radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8; 11/30: 0.6; 12/20 1.4; 1/10 1.8; 1/31 2.2; 2/28 2.6; 4/10 2.8
MSS, KRAS G12D
10/17: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 (-75%), 5 x 3 (-40%). 5.1 CM from AV
10/17: LAR, Temp Ileostomy, Path Complete Response
CapeOx 8 cycles 12/17-6/18

sdino
Posts: 59
Joined: Tue Mar 28, 2017 5:32 pm

Re: anyone here with Kras T53 mutation

Postby sdino » Fri Jun 08, 2018 10:25 am

Here is my take on the TP53's: So... Healthy P53’s fight cancerous DNA. But when they get sick or mutated they stop fighting the bad cells. So there is efforts to boost the healthy P53’s to fight harder but years of testing, nothing has made it to the Market. Researchers are trying to restore the P53’s back to their normal state to carry-on the fight. They are finding drugs that bind to and prop up copies of mutated p53, restoring its shape and ability to carry out its job. One such drug has already passed an early stage safety trial in humans, and a more advanced clinical trial is now underway in Europe. The payoff could be big, however. Not only could the strategy treat many kinds of cancer, but just a handful of drugs might be enough,
particularly when coupled with chemotherapy drugs that induce the tumor cell damage to which p53 responds. P53 mutations tend to be clustered in the core of the protein, where it binds to DNA.

Another protein, MDM2, latches onto P53 molecules and destroys them, keeping their numbers in check. But this control mechanism can fail in multiple ways. For starters, when p53 itself is mutated, MDM2 cannot attack it. As a result, the malfunctioning protein builds up in cells unchecked and keeps the remaining healthy p53 from doing its job. Without the genome’s guardian on patrol, precancerous cells survive and reproduce. This gives them the opportunity to build up the additional mutations they need to become fully malignant.

At this point, it’s slightly unclear which if any P53 stabilization strategy will pan out. They are trying like hell... with some promising results.

SIDE NOTES
- ovarian cancer, almost always has p53 mutations.
- Healthy P53’s = Good to fight Cancer
- Mutated P53’s = Not good, they are essentially working on restoring them back to healthy P53’s. Hope I explained this OK, hopefully Im not to far off base with my understanding ? I will post another question regarding trials of P53's vs. also worrying about other mutations (Kras, Braf, ect.. ) as the waters get
Caregiver for Wife 52 yrs old
DX:11/16-CC sigmoid colon
Lung Mets: Bilateral ranging 4mm-1.5cm
MSS, KRAS-mut G12D; TP53
Completed 12 rounds Folfox/Avastin + Oxi 11/16 to 5/17, 8/17 Start Xeloda + Avastin
CT Scans: 5/17 colon & lung met shrinkage,11/17 and 1/18 slight progression lungs/colon; 5/18 stable lungs/colon
NCI YOUNGER TIL Trial NCT03412877 - 1/18 VATs lung surgery 2 mets wedge resect
CEA: 16 - 11/16; 0.6 - 5/17; 3.0 - 11/17; 4.4 - 1/18; 5.7 - 2/18; 4.9 - 3/18, 4.0 - 5/18

NHMike
Posts: 1558
Joined: Fri Jul 21, 2017 3:43 am

Re: anyone here with Kras T53 mutation

Postby NHMike » Fri Jun 08, 2018 10:36 am

sdino wrote:Here is my take on the TP53's: So... Healthy P53’s fight cancerous DNA. But when they get sick or mutated they stop fighting the bad cells. So there is efforts to boost the healthy P53’s to fight harder but years of testing, nothing has made it to the Market. Researchers are trying to restore the P53’s back to their normal state to carry-on the fight. They are finding drugs that bind to and prop up copies of mutated p53, restoring its shape and ability to carry out its job. One such drug has already passed an early stage safety trial in humans, and a more advanced clinical trial is now underway in Europe. The payoff could be big, however. Not only could the strategy treat many kinds of cancer, but just a handful of drugs might be enough,
particularly when coupled with chemotherapy drugs that induce the tumor cell damage to which p53 responds. P53 mutations tend to be clustered in the core of the protein, where it binds to DNA.

Another protein, MDM2, latches onto P53 molecules and destroys them, keeping their numbers in check. But this control mechanism can fail in multiple ways. For starters, when p53 itself is mutated, MDM2 cannot attack it. As a result, the malfunctioning protein builds up in cells unchecked and keeps the remaining healthy p53 from doing its job. Without the genome’s guardian on patrol, precancerous cells survive and reproduce. This gives them the opportunity to build up the additional mutations they need to become fully malignant.

At this point, it’s slightly unclear which if any P53 stabilization strategy will pan out. They are trying like hell... with some promising results.

SIDE NOTES
- ovarian cancer, almost always has p53 mutations.
- Healthy P53’s = Good to fight Cancer
- Mutated P53’s = Not good, they are essentially working on restoring them back to healthy P53’s. Hope I explained this OK, hopefully Im not to far off base with my understanding ? I will post another question regarding trials of P53's vs. also worrying about other mutations (Kras, Braf, ect.. ) as the waters get


Great explanation.
6/17: ER rectal bleeding; Colonoscopy
7/17: Stage 3B rectal. T3N1bM0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6, 5 x 5
7/17-9/17: Xeloda +radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8; 11/30: 0.6; 12/20 1.4; 1/10 1.8; 1/31 2.2; 2/28 2.6; 4/10 2.8
MSS, KRAS G12D
10/17: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 (-75%), 5 x 3 (-40%). 5.1 CM from AV
10/17: LAR, Temp Ileostomy, Path Complete Response
CapeOx 8 cycles 12/17-6/18

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GrouseMan
Posts: 750
Joined: Mon Aug 12, 2013 12:30 pm
Location: SE Michigan USA

Re: anyone here with Kras T53 mutation

Postby GrouseMan » Fri Jun 08, 2018 4:04 pm

The Letters represent the amino acid substitution in the protein or in this case the Kras Gene. So for Kras G12D that is - in position 12 of the Kras Gene the normal wild type has a Glycine (Abbreviated G) that has been changed to an Aspartic Acid (abbreviated D) in the mutation. These two amino acids are very different in shape and as a result greatly effects the binding of inhibitors of KRAS. Kras G12D is the most common mutation of Kras but there are others. I believe about 30% of colon cancers have mutations in Kras.

Regards,

GrouseMan
DW 53 dx Jun 2013
CT mets Liver Spleen lung. IVb CEA~110
Jul 2013 Sig Resct
8/13 FolFox,Avastin 12Tx mild sfx, Ongoing 5-FU Avastin every 3 wks.
CEA: good marker
7/7/14 CT Can't see the spleen Mets.
8/16/15 CEA Up, CT new abdominal mets. Iri, 5-FU, Avastin every 2 wks.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
1/17 CEA up again dropped from Trial, Mets growth 4-6 mm in abdomen
5/2/17 Failed second trial, Hospitalized 15 days 5/11. Home Hospice 5/26, at peace 6/4/2017

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LPL
Posts: 410
Joined: Fri Apr 22, 2016 12:49 am
Location: Europe

Re: anyone here with Kras T53 mutation

Postby LPL » Fri Jun 08, 2018 4:38 pm

Dear GrouseMan,
Do you know if I should care that my husband has another kind of Kras? See my signature, ”Kras G13D”. We do not know about any other mutations, like T53 etc. No test done for that as far as I know.
DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED for now :D
:!: Steroid induced hyperglycemia dx after 3chemo .. hospitalized, insulin -> Metformin
Surgeries (open):
3/18 Emergency colostomy 5/23 Primary+gallbl+colostomy reversal (+port) 9/01 Liver mets

NHMike
Posts: 1558
Joined: Fri Jul 21, 2017 3:43 am

Re: anyone here with Kras T53 mutation

Postby NHMike » Fri Jun 08, 2018 6:53 pm

LPL wrote:Dear GrouseMan,
Do you know if I should care that my husband has another kind of Kras? See my signature, ”Kras G13D”. We do not know about any other mutations, like T53 etc. No test done for that as far as I know.


KRAS G13D would be similar to G12D, it's just in the 13th Codon instead of the 12th.

I think that most Genomic Tumor Testing is done using Next Generation Sequencing and this scans for all known mutations. My report listed what I had that was known. It found two other abnormalities that were unknown - those I'm not going to worry about. I think that the one-at-a-time was with older sequencing machines.
6/17: ER rectal bleeding; Colonoscopy
7/17: Stage 3B rectal. T3N1bM0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6, 5 x 5
7/17-9/17: Xeloda +radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8; 11/30: 0.6; 12/20 1.4; 1/10 1.8; 1/31 2.2; 2/28 2.6; 4/10 2.8
MSS, KRAS G12D
10/17: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 (-75%), 5 x 3 (-40%). 5.1 CM from AV
10/17: LAR, Temp Ileostomy, Path Complete Response
CapeOx 8 cycles 12/17-6/18

User avatar
LPL
Posts: 410
Joined: Fri Apr 22, 2016 12:49 am
Location: Europe

Re: anyone here with Kras T53 mutation

Postby LPL » Fri Jun 08, 2018 7:56 pm

NHMike wrote:
KRAS G13D would be similar to G12D, it's just in the 13th Codon instead of the 12th.

Well.. thank you for replying Mike.
I do understand it is in a different codon. Not sure it is “similar to G12D” though.. I have seen research where they say there are differences between Kras codon 12 and 13 - in respons to treatments for example. Also some trials have specific Kras xxxx mentioned so why do they have that if it is ‘the same’?
Maybe all KRAS are not the same?
That is why I asked GrouseMan since he is a researcher.
DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED for now :D
:!: Steroid induced hyperglycemia dx after 3chemo .. hospitalized, insulin -> Metformin
Surgeries (open):
3/18 Emergency colostomy 5/23 Primary+gallbl+colostomy reversal (+port) 9/01 Liver mets

NHMike
Posts: 1558
Joined: Fri Jul 21, 2017 3:43 am

Re: anyone here with Kras T53 mutation

Postby NHMike » Fri Jun 08, 2018 8:01 pm

LPL wrote:
NHMike wrote:
KRAS G13D would be similar to G12D, it's just in the 13th Codon instead of the 12th.

Well.. thank you for replying Mike.
I do understand it is in a different codon. Not sure it is “similar to G12D” though.. I have seen research where they say there are differences between Kras codon 12 and 13 - in respons to treatments for example. Also some trials have specific Kras xxxx mentioned so why do they have that if it is ‘the same’?
Maybe all KRAS are not the same?
That is why I asked GrouseMan since he is a researcher.


I agree that all of these things are different. G12V seems to be more aggressive than G12D. And G12D is known to work with TIL with certain Alleles present.

I've done a moderate amount of research on G12D because I have it and G13D because someone else that I know has it.

There weren't a lot of treatment options for these things until the TIL stuff came along.
6/17: ER rectal bleeding; Colonoscopy
7/17: Stage 3B rectal. T3N1bM0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6, 5 x 5
7/17-9/17: Xeloda +radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8; 11/30: 0.6; 12/20 1.4; 1/10 1.8; 1/31 2.2; 2/28 2.6; 4/10 2.8
MSS, KRAS G12D
10/17: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 (-75%), 5 x 3 (-40%). 5.1 CM from AV
10/17: LAR, Temp Ileostomy, Path Complete Response
CapeOx 8 cycles 12/17-6/18

NHMike
Posts: 1558
Joined: Fri Jul 21, 2017 3:43 am

Re: anyone here with Kras T53 mutation

Postby NHMike » Fri Jun 08, 2018 8:17 pm

LPL wrote:
NHMike wrote:
KRAS G13D would be similar to G12D, it's just in the 13th Codon instead of the 12th.

Well.. thank you for replying Mike.
I do understand it is in a different codon. Not sure it is “similar to G12D” though.. I have seen research where they say there are differences between Kras codon 12 and 13 - in respons to treatments for example. Also some trials have specific Kras xxxx mentioned so why do they have that if it is ‘the same’?
Maybe all KRAS are not the same?
That is why I asked GrouseMan since he is a researcher.


I think that you can get some appreciation in the many articles out there on the "undruggable" aspect of KRAS. Drugmakers have been working on fighting KRAS for 30 years and have been largely unsuccessful which is why we wind up using 5FU, Oxaliplatin and generally using awful chemo drugs to treat it. TIL is very promising. You can go around looking at research articles on KRAS G12D or G12V or G13D to see what's being done or attempts to solve them in the past. I like to search Twitter for research articles on this stuff because a lot of researchers or their organizations or even ASCO post their abstracts there.

I chatted with the pathologist (also HMS professor) that wrote my Genomic Tumor report and he told me that there were no targeted therapies available for me. I mentioned TIL and he indicated that the odds that I would have the indicated Allele were very small. Though the paper that he read might not have talked about the other Alleles that worked - my odds on one of the other alleles was about 30%.
6/17: ER rectal bleeding; Colonoscopy
7/17: Stage 3B rectal. T3N1bM0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6, 5 x 5
7/17-9/17: Xeloda +radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8; 11/30: 0.6; 12/20 1.4; 1/10 1.8; 1/31 2.2; 2/28 2.6; 4/10 2.8
MSS, KRAS G12D
10/17: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 (-75%), 5 x 3 (-40%). 5.1 CM from AV
10/17: LAR, Temp Ileostomy, Path Complete Response
CapeOx 8 cycles 12/17-6/18

Jackar0e
Posts: 10
Joined: Fri Feb 10, 2017 8:55 pm
Facebook Username: Amy Cremisio
Location: Waterford, NY

Re: anyone here with Kras T53 mutation

Postby Jackar0e » Sat Jun 09, 2018 1:54 pm

Thank you everyone so so very much!!!
44yrs old /Female
DX: Rectal Cancer
Tumor Location: If RC lower rectum,colon
Tumor type: carcinoma,
Tumor size 13mm

G1: Well differentiated
Stage : Stage IV
Mets: Liver
Baseline CEA value
Lymphovascular invasion : present


KRAS +

Chemotherapy XELOX, CAPEOX, FOLFOX,

Jackar0e
Posts: 10
Joined: Fri Feb 10, 2017 8:55 pm
Facebook Username: Amy Cremisio
Location: Waterford, NY

Re: anyone here with Kras T53 mutation

Postby Jackar0e » Sat Jun 09, 2018 2:09 pm

GrouseMan wrote:The Letters represent the amino acid substitution in the protein or in this case the Kras Gene. So for Kras G12D that is - in position 12 of the Kras Gene the normal wild type has a Glycine (Abbreviated G) that has been changed to an Aspartic Acid (abbreviated D) in the mutation. These two amino acids are very different in shape and as a result greatly effects the binding of inhibitors of KRAS. Kras G12D is the most common mutation of Kras but there are others. I believe about 30% of colon cancers have mutations in Kras.

Regards,

GrouseMan



Thank you so much that is very well put, My oncologist dose not seem hopeful. I looked at the letters and mine are G12S stupid ? but why the S and not the D?? they are trying one last chemo of oxy and 5FU then I guess clinical Trial :( I appreciate all the help I can get. We are the best advocates for ourselves :)
44yrs old /Female
DX: Rectal Cancer
Tumor Location: If RC lower rectum,colon
Tumor type: carcinoma,
Tumor size 13mm

G1: Well differentiated
Stage : Stage IV
Mets: Liver
Baseline CEA value
Lymphovascular invasion : present


KRAS +

Chemotherapy XELOX, CAPEOX, FOLFOX,

NHMike
Posts: 1558
Joined: Fri Jul 21, 2017 3:43 am

Re: anyone here with Kras T53 mutation

Postby NHMike » Sat Jun 09, 2018 2:17 pm

Jackar0e wrote:
GrouseMan wrote:The Letters represent the amino acid substitution in the protein or in this case the Kras Gene. So for Kras G12D that is - in position 12 of the Kras Gene the normal wild type has a Glycine (Abbreviated G) that has been changed to an Aspartic Acid (abbreviated D) in the mutation. These two amino acids are very different in shape and as a result greatly effects the binding of inhibitors of KRAS. Kras G12D is the most common mutation of Kras but there are others. I believe about 30% of colon cancers have mutations in Kras.

Regards,

GrouseMan



Thank you so much that is very well put, My oncologist dose not seem hopeful. I looked at the letters and mine are G12S stupid ? but why the S and not the D?? they are trying one last chemo of oxy and 5FU then I guess clinical Trial :( I appreciate all the help I can get. We are the best advocates for ourselves :)


The KRAS G12S mutation arises from a single nucleotide change (c.34G>A) and results in an amino acid substitution of the glycine (G) at position 12 by a serine (S).

http://targetedcancercare.massgeneral.o ... S-(c-34G-A).aspx
6/17: ER rectal bleeding; Colonoscopy
7/17: Stage 3B rectal. T3N1bM0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6, 5 x 5
7/17-9/17: Xeloda +radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8; 11/30: 0.6; 12/20 1.4; 1/10 1.8; 1/31 2.2; 2/28 2.6; 4/10 2.8
MSS, KRAS G12D
10/17: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 (-75%), 5 x 3 (-40%). 5.1 CM from AV
10/17: LAR, Temp Ileostomy, Path Complete Response
CapeOx 8 cycles 12/17-6/18

boxhill
Posts: 90
Joined: Fri Apr 06, 2018 11:40 am

Re: anyone here with Kras T53 mutation

Postby boxhill » Sat Jun 09, 2018 2:39 pm

The report on my tumor from Dana Farber/Brigham Women's says:

KRAS c.35G>A (p.G12D), exon 2 - in 18% of 321 reads*
TP53 c.993+2T>C () - **TP53 is a tumor suppressor gene. TP53 mutations are
frequently seen in colorectal adenocarcinoma (PMID: 22810696).

Thanks to this thread I now have a better idea of what those mean.
F, 64 at DX CRC Stage IV (or "3 1/2" per Dana Farber consult, LOL)
3/17/18 blockage, emergency surgery, r hemicolectomy
11 of 25 nodes
5 of 5 mesentery nodes, matted
0.5 cm sub-capsular liver met removed
pT3 pN2b pM1
Neg CEA, neg BRAF, mut KRAS, germline mut ATM
dMMR, MSI-H, Neg for Lynch
5/4/18 FOLFOX started
Added Neulasta 6/28/18
7/9/18 CT scans show no masses or enlarged nodes, 2mm indeterminate lung nodule

NHMike
Posts: 1558
Joined: Fri Jul 21, 2017 3:43 am

Re: anyone here with Kras T53 mutation

Postby NHMike » Sat Jun 09, 2018 3:00 pm

boxhill wrote:The report on my tumor from Dana Farber/Brigham Women's says:

KRAS c.35G>A (p.G12D), exon 2 - in 18% of 321 reads*
TP53 c.993+2T>C () - **TP53 is a tumor suppressor gene. TP53 mutations are
frequently seen in colorectal adenocarcinoma (PMID: 22810696).

Thanks to this thread I now have a better idea of what those mean.

But I seem to have missed something: what is TIL?


Tumor Infiltrating Lymphocytes. Work done at NCI with one of the members here to cure KRAS G12D.

KRAS is one of the most frequently mutated proto-oncogenes in human cancers. The dominant
oncogenic mutations of KRAS are single amino acid substitutions at codon 12, in particular G12D
and G12V present in 60–70% of pancreatic cancers and 20–30% of colorectal cancers. The
consistency, frequency, and tumor specificity of these “neo-antigens” make them attractive
therapeutic targets. Recent data associates T cells that target mutated antigens with clinical
immunotherapy responses in patients with metastatic melanoma, lung cancer, or
cholangiocarcinoma. Using HLA-peptide prediction algorithms, we noted that HLA-A*11:01
could potentially present mutated KRAS variants. By immunizing HLA-A*11:01 transgenic mice,
we generated murine T cells and subsequently isolated T-cell receptors (TCRs) highly reactive to
the mutated KRAS variants G12V and G12D. Peripheral blood lymphocytes (PBLs) transduced
with these TCRs could recognize multiple HLA-A*11:01+ tumor lines bearing the appropriate
KRAS mutations. In a xenograft model of large established tumor, adoptive transfer of these
transduced PBLs reactive with an HLA-A*11:01, G12D-mutated pancreatic cell line could
significantly reduce its growth in NSG mice (P = 0.002). The success of adoptive transfer of TCR-
engineered T cells against melanoma and other cancers support clinical trials with these T cells
that recognize mutated KRAS in patients with a variety of common cancer types.


https://www.ncbi.nlm.nih.gov/pmc/articl ... 747004.pdf

We identified a polyclonal CD8+ T-cell response against mutant KRAS G12D in tumor-infiltrating
lymphocytes obtained from a patient with metastatic colorectal cancer. We observed objective
regression of all seven lung metastases after the infusion of approximately 1.11×10 11 HLA-
C*08:02–restricted tumor-infiltrating lymphocytes that were composed of four different T-cell
clonotypes that specifically targeted KRAS G12D. However, one of these lesions had progressed
on evaluation 9 months after therapy. The lesion was resected and found to have lost the
chromosome 6 haplotype encoding the HLA-C*08:02 class I major histocompatibility complex
(MHC) molecule. The loss of expression of this molecule provided a direct mechanism of tumor
immune evasion. Thus, the infusion of CD8+ cells targeting mutant KRAS mediated effective
antitumor immunotherapy against a cancer that expressed mutant KRAS G12D and HLA-
C*08:02.


https://www.ncbi.nlm.nih.gov/pmc/articl ... 836415.pdf
6/17: ER rectal bleeding; Colonoscopy
7/17: Stage 3B rectal. T3N1bM0. 5.2 x 4.5 x 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6, 5 x 5
7/17-9/17: Xeloda +radiation
7/5: CEA 2.7; 8/16: 1.9; 9/8: 1.8; 11/30: 0.6; 12/20 1.4; 1/10 1.8; 1/31 2.2; 2/28 2.6; 4/10 2.8
MSS, KRAS G12D
10/17: 2.7 x 2.2 x 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 (-75%), 5 x 3 (-40%). 5.1 CM from AV
10/17: LAR, Temp Ileostomy, Path Complete Response
CapeOx 8 cycles 12/17-6/18


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