# US 11,897,933 B2 · Anti-KRAS-G12D T cell receptors

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- Number: US 11,897,933 B2
- Document ID: US11897933B2
- Status: Granted
- Kind: B2
- Application number: 17/345,390
- Filed: 2021-06-11
- Published: 2021-09-30
- Granted: 2024-02-13
- Earliest claimed: 2016-08-02
- Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services
- Applicants: The United States of America,as represented by the Secretary,Department of Health and Human Services
- Inventors: Eric Tran; Yong-Chen Lu; Anna Pasetto; Paul F. Robbins; Steven A. Rosenberg; Zhili Zheng
- Web page: https://patentgrep.com/patent/US11897933B2

## CPC

- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/32: T-cell receptors [TCR]
- A61K 40/4201: {Neoantigens}
- A61P 35/00: Antineoplastic agents
- C07K 14/82: Translation products from oncogenes
- C12N 15/85: for animal cells
- G01N 33/57557: {of other specific parts of the body, e.g. brain}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C12N 2015/8518: {expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles}
- G01N 2333/7051: T-cell receptor (TcR)-CD3 complex
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) presented in the context of an HLA-Cw*0802 molecule. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

## Claims

### Claim 1

An isolated or purified nucleic acid comprising a nucleotide sequence encoding a TCR comprising:
(i) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 15 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 16;
(ii) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 23 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 24;
(iii) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 31 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 32;
(iv) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 39 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 40;
(v) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO: 15 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO: 16;
(vi) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO: 23 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO: 24;
(vii) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO: 31 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO: 32; or
(viii) an amino acid sequence at least 99% identical to amino acids 21-132 of SEQ ID NO: 39 and an amino acid sequence at least 99% identical to amino acids 22-130 of SEQ ID NO: 40.

### Claim 2 (depends on 1)

The isolated or purified nucleic acid of claim 1, wherein the TCR comprises:
(i) an amino acid sequence comprising amino acids 20-129 of SEQ ID NO: 15 and an amino acid sequence comprising amino acids 22-133 of SEQ ID NO: 16;
(ii) an amino acid sequence comprising amino acids 20-129 of SEQ ID NO: 23 and an amino acid sequence comprising amino acids 22-133 of SEQ ID NO: 24;
(iii) an amino acid sequence comprising amino acids 20-129 of SEQ ID NO: 31 and an amino acid sequence comprising amino acids 22-133 of SEQ ID NO: 32; or
(iv) an amino acid sequence comprising amino acids 21-132 of SEQ ID NO: 39 and an amino acid sequence comprising amino acids 22-130 of SEQ ID NO: 40.

### Claim 3 (depends on 1)

The isolated or purified nucleic acid of claim 1, wherein the TCR comprises:
(A) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 46, wherein:
(i) X at position 48 of SEQ ID NO: 46 is Thr or Cys;
(ii) X at position 112 of SEQ ID NO: 46 is Ser, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
(iii) X at position 114 of SEQ ID NO: 46 is Met, Ala, Val, Leu, Ile, Pro, Phe, or Trp; and
(iv) X at position 115 of SEQ ID NO: 46 is Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
and
(B) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 47, wherein X at position 57 of SEQ ID NO: 47 is Ser or Cys.

### Claim 4 (depends on 1)

The isolated or purified nucleic acid of claim 1, wherein the TCR comprises:
(A) the amino acid sequence of SEQ ID NO: 46, wherein:
(i) X at position 48 of SEQ ID NO: 46 is Thr or Cys;
(ii) X at position 112 of SEQ ID NO: 46 is Ser, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
(iii) X at position 114 of SEQ ID NO: 46 is Met, Ala, Val, Leu, Ile, Pro, Phe, or Trp; and
(iv) X at position 115 of SEQ ID NO: 46 is Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
and
(B) the amino acid sequence of SEQ ID NO: 47, wherein X at position 57 of SEQ ID NO: 47 is Ser or Cys.

### Claim 5 (depends on 1)

The isolated or purified nucleic acid of claim 1, wherein the TCR comprises:
(1) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 50 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 51;
(2) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 52 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 53;
(3) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 54 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 55;
(4) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 56 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 57;
(5) an amino acid sequence at least 99% identical to amino acids 20-266 of SEQ ID NO: 50 and an amino acid sequence at least 99% identical to amino acids 22-306 of SEQ ID NO: 51;
(6) an amino acid sequence at least 99% identical to amino acids 20-266 of SEQ ID NO: 52 and an amino acid sequence at least 99% identical to amino acids 22-306 of SEQ ID NO: 53;
(7) an amino acid sequence at least 99% identical to amino acids 20-266 of SEQ ID NO: 54 and an amino acid sequence at least 99% identical to amino acids 22-306 of SEQ ID NO: 55; or
(8) an amino acid sequence at least 99% identical to amino acids 21-269 of SEQ ID NO: 56 and an amino acid sequence at least 99% identical to amino acids 22-303 of SEQ ID NO: 57.

### Claim 6 (depends on 1)

The isolated or purified nucleic acid of claim 1, wherein the TCR comprises:
(1) an amino acid sequence comprising amino acids 20-266 of SEQ ID NO: 50 and an amino acid sequence comprising amino acids 22-306 of SEQ ID NO: 51;
(2) an amino acid sequence comprising amino acids 20-266 of SEQ ID NO: 52 and an amino acid sequence comprising amino acids 22-306 of SEQ ID NO: 53;
(3) an amino acid sequence comprising amino acids 20-266 of SEQ ID NO: 54 and an amino acid sequence comprising amino acids 22-306 of SEQ ID NO: 55; or
(4) an amino acid sequence comprising amino acids 21-269 of SEQ ID NO: 56 and an amino acid sequence comprising amino acids 22-303 of SEQ ID NO: 57.

### Claim 7

An isolated or purified nucleic acid comprising a nucleotide sequence encoding a polypeptide comprising:
(i) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 15 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 16;
(ii) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 23 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 24;
(iii) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 31 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 32;
(iv) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 39 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 40;
(v) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO: 15 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO: 16;
(vi) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO: 23 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO: 24;
(vii) an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO: 31 and an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO: 32; or
(viii) an amino acid sequence at least 99% identical to amino acids 21-132 of SEQ ID NO: 39 and an amino acid sequence at least 99% identical to amino acids 22-130 of SEQ ID NO: 40.

### Claim 8 (depends on 7)

The isolated or purified nucleic acid of claim 7, wherein the polypeptide comprises:
(i) an amino acid sequence comprising amino acids 20-129 of SEQ ID NO: 15 and an amino acid sequence comprising amino acids 22-133 of SEQ ID NO: 16;
(ii) an amino acid sequence comprising amino acids 20-129 of SEQ ID NO: 23 and an amino acid sequence comprising amino acids 22-133 of SEQ ID NO: 24;
(iii) an amino acid sequence comprising amino acids 20-129 of SEQ ID NO: 31 and an amino acid sequence comprising amino acids 22-133 of SEQ ID NO: 32; or
(iv) an amino acid sequence comprising amino acids 21-132 of SEQ ID NO: 39 and an amino acid sequence comprising amino acids 22-130 of SEQ ID NO: 40.

### Claim 9 (depends on 7)

The isolated or purified nucleic acid of claim 7, wherein the polypeptide comprises:
(A) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 46, wherein
(i) X at position 48 of SEQ ID NO: 46 is Thr or Cys;
(ii) X at position 112 of SEQ ID NO: 46 is Ser, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
(iii) X at position 114 of SEQ ID NO: 46 is Met, Ala, Val, Leu, Ile, Pro, Phe, or Trp; and
(iv) X at position 115 of SEQ ID NO: 46 is Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
and
(B) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 47, wherein X at position 57 of SEQ ID NO: 47 is Ser or Cys.

### Claim 10 (depends on 7)

The isolated or purified nucleic acid of claim 7, wherein the polypeptide comprises:
(A) the amino acid sequence of SEQ ID NO: 46, wherein
(i) X at position 48 of SEQ ID NO: 46 is Thr or Cys;
(ii) X at position 112 of SEQ ID NO: 46 is Ser, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
(iii) X at position 114 of SEQ ID NO: 46 is Met, Ala, Val, Leu, Ile, Pro, Phe, or Trp;
and
(iv) X at position 115 of SEQ ID NO: 46 is Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
and
(B) the amino acid sequence of SEQ ID NO: 47, wherein X at position 57 of SEQ ID NO: 47 is Ser or Cys.

### Claim 11 (depends on 7)

The isolated or purified nucleic acid of claim 7, wherein the polypeptide comprises:
(1) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 50 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 51;
(2) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 52 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 53;
(3) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 54 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 55;
(4) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 56 and an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 57;
(5) an amino acid sequence at least 99% identical to amino acids 20-266 of SEQ ID NO: 50 and an amino acid sequence at least 99% identical to amino acids 22-306 of SEQ ID NO: 51;
(6) an amino acid sequence at least 99% identical to amino acids 20-266 of SEQ ID NO: 52 and an amino acid sequence at least 99% identical to amino acids 22-306 of SEQ ID NO: 53;
(7) an amino acid sequence at least 99% identical to amino acids 20-266 of SEQ ID NO: 54 and an amino acid sequence at least 99% identical to amino acids 22-306 of SEQ ID NO: 55; or
(8) an amino acid sequence at least 99% identical to amino acids 21-269 of SEQ ID NO: 56 and an amino acid sequence at least 99% identical to amino acids 22-303 of SEQ ID NO: 57.

### Claim 12 (depends on 7)

The isolated or purified nucleic acid of claim 7, wherein the polypeptide comprises:
(1) an amino acid sequence comprising amino acids 20-266 of SEQ ID NO: 50 and an amino acid sequence comprising amino acids 22-306 of SEQ ID NO: 51;
(2) an amino acid sequence comprising amino acids 20-266 of SEQ ID NO: 52 and an amino acid sequence comprising amino acids 22-306 of SEQ ID NO: 53;
(3) an amino acid sequence comprising amino acids 20-266 of SEQ ID NO: 54 and an amino acid sequence comprising amino acids 22-306 of SEQ ID NO: 55; or
(4) an amino acid sequence comprising amino acids 21-269 of SEQ ID NO: 56 and an amino acid sequence comprising amino acids 22-303 of SEQ ID NO: 57.

### Claim 13

An isolated or purified nucleic acid comprising a nucleotide sequence encoding a protein comprising a first polypeptide chain and a second polypeptide chain, wherein
(i) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 15 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 16;
(ii) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 23 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 24;
(iii) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 31 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 32;
(iv) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 39 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 40;
(v) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO: 15 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO: 16;
(vi) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO: 23 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO: 24;
(vii) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 20-129 of SEQ ID NO: 31 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-133 of SEQ ID NO: 32; or
(viii) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 21-132 of SEQ ID NO: 39 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-130 of SEQ ID NO: 40.

### Claim 14 (depends on 13)

The isolated or purified nucleic acid of claim 13, wherein
(i) the first polypeptide chain comprises amino acids 20-129 of SEQ ID NO: 15 and the second polypeptide chain comprises amino acids 22-133 of SEQ ID NO: 16;
(ii) the first polypeptide chain comprises amino acids 20-129 of SEQ ID NO: 23 and the second polypeptide chain comprises amino acids 22-133 of SEQ ID NO: 24;
(iii) the first polypeptide chain comprises amino acids 20-129 of SEQ ID NO: 31 and the second polypeptide chain comprises amino acids 22-133 of SEQ ID NO: 32; or
(iv) the first polypeptide chain comprises amino acids 21-132 of SEQ ID NO: 39 and the second polypeptide chain comprises amino acids 22-130 of SEQ ID NO: 40.

### Claim 15 (depends on 13)

The isolated or purified nucleic acid of claim 13, wherein
(A) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 46, wherein:
(i) X at position 48 of SEQ ID NO: 46 is Thr or Cys;
(ii) X at position 112 of SEQ ID NO: 46 is Ser, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
(iii) X at position 114 of SEQ ID NO: 46 is Met, Ala, Val, Leu, Ile, Pro, Phe, or Trp;
and
(iv) X at position 115 of SEQ ID NO: 46 is Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
and
(B) the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 47, wherein X at position 57 of SEQ ID NO: 47 is Ser or Cys.

### Claim 16 (depends on 13)

The isolated or purified nucleic acid of claim 13, wherein
(A) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 46, wherein:
(i) X at position 48 of SEQ ID NO: 46 is Thr or Cys;
(ii) X at position 112 of SEQ ID NO: 46 is Ser, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
(iii) X at position 114 of SEQ ID NO: 46 is Met, Ala, Val, Leu, Ile, Pro, Phe, or Trp;
and
(iv) X at position 115 of SEQ ID NO: 46 is Gly, Ala, Val, Leu, Ile, Pro, Phe, Met, or Trp;
and
(B) the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 47, wherein X at position 57 of SEQ ID NO: 47 is Ser or Cys.

### Claim 17 (depends on 13)

The isolated or purified nucleic acid of claim 13, wherein
(1) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 50 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 51;
(2) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 52 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 53;
(3) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 54 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 55;
(4) the first polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 56 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 57;
(5) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 20-266 of SEQ ID NO: 50 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-306 of SEQ ID NO: 51;
(6) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 20-266 of SEQ ID NO: 52 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-306 of SEQ ID NO: 53;
(7) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 20-266 of SEQ ID NO: 54 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-306 of SEQ ID NO: 55; or
(8) the first polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 21-269 of SEQ ID NO: 56 and the second polypeptide chain comprises an amino acid sequence at least 99% identical to amino acids 22-303 of SEQ ID NO: 57.

### Claim 18 (depends on 13)

The isolated or purified nucleic acid of claim 13, wherein
(1) the first polypeptide chain comprises amino acids 20-266 of SEQ ID NO: 50 and the second polypeptide chain comprises amino acids 22-306 of SEQ ID NO: 51;
(2) the first polypeptide chain comprises amino acids 20-266 of SEQ ID NO: 52 and the second polypeptide chain comprises amino acids 22-306 of SEQ ID NO: 53;
(3) the first polypeptide chain comprises amino acids 20-266 of SEQ ID NO: 54 and the second polypeptide chain comprises amino acids 22-306 of SEQ ID NO: 55; or
(4) the first polypeptide chain comprises amino acids 21-269 of SEQ ID NO: 56 and the second polypeptide chain comprises amino acids 22-303 of SEQ ID NO: 57.

### Claim 19 (depends on 1)

A recombinant expression vector comprising the nucleic acid of claim 1.

### Claim 20 (depends on 19)

An isolated or purified host cell comprising the expression vector of claim 19.

### Claim 21 (depends on 19)

A population of cells comprising the expression vector of claim 19.

### Claim 22 (depends on 21)

A pharmaceutical composition comprising the population of cells of claim 21 and a pharmaceutically acceptable carrier.

### Claim 23 (depends on 1)

An isolated or purified host cell comprising the nucleic acid of claim 1.

### Claim 24 (depends on 1)

A population of cells comprising the nucleic acid of claim 1.

### Claim 25 (depends on 24)

A pharmaceutical composition comprising the population of cells of claim 24 and a pharmaceutically acceptable carrier.

### Claim 26 (depends on 3)

An isolated or purified host cell comprising the nucleic acid of claim 3.

### Claim 27 (depends on 3)

A population of cells comprising the nucleic acid of claim 3.

### Claim 28 (depends on 27)

A pharmaceutical composition comprising the population of cells of claim 27 and a pharmaceutically acceptable carrier.

### Claim 29 (depends on 23)

A method of treating a KRAS G12D-expressing cancer in a mammal, comprising administering to the mammal the host cell of claim 23 in an amount effective to treat the KRAS G12D-expressing cancer in the mammal.

### Claim 30 (depends on 24)

A method of treating a KRAS G12D-expressing cancer in a mammal, comprising administering to the mammal the population of cells of claim 24 in an amount effective to treat the KRAS G12D-expressing cancer in the mammal.

### Claim 31 (depends on 25)

A method of treating a KRAS G12D-expressing cancer in a mammal, comprising administering to the mammal the pharmaceutical composition of claim 25 in an amount effective to treat the KRAS G12D-expressing cancer in the mammal.

### Claim 32 (depends on 19)

A method of producing a host cell expressing a TCR comprising contacting a cell with the recombinant expression vector of claim 19 under conditions that allow introduction of the vector into the cell.

### Claim 33 (depends on 19)

A method of producing a population of cells expressing a TCR comprising contacting a population of cells with the recombinant expression vector of claim 19 under conditions that allow introduction of the vector into the population of cells.

### Claim 34 (depends on 23)

A method of producing a TCR comprising culturing the host cell of claim 23 so that the TCR is produced.

### Claim 35 (depends on 24)

A method of producing a TCR comprising culturing the population of cells of claim 24 so that the TCR is produced.