Combination of protein vaccine and mesenchymal stem cells for treating cancer
A method for inhibiting growth and/or metastasis of a tumor in a mammal is disclosed. The method comprises administering to a mammal in need thereof an effective amount of stem cells comprising a transgene encoding at least one oncogenic protein, wherein the stem cells are immortal and show no signs of neoplastic transformation; and administering to the mammal a vaccine composition comprising an effective amount of at least one immunogenic protein capable of eliciting at least one antibody specific against the at least one oncogenic protein, and thereby inhibiting growth and/or metastasis of a tumor in the mammal. A therapeutic kit for inhibiting growth and/or metastasis of a tumor in a mammal is also disclosed.
1. A method for inhibiting growth and/or metastasis of a cancer cell, cornprising:
administering to a mammal in need thereof an effective amount of mesenchymal stem cells comprising a transgene encoding human papillomavirus (HPV) oncogenic protein selected from the group consisting of HPV E7, HPV E6 and a combination thereof, wherein the mesenchymal stem cells are immortal and show no signs of neoplastic transformation;
administering to the mammal a vaccine composition comprising an effective amount of an immunogenic protein capable of eliciting an antibody specific against the HPV oncogenic protein selected from the group consisting of HPV E7, HPV E6 and a combination thereof;
wherein the mesenchymal stem cells fuse with the cancer cell in the mammal, and wherein the fusion results in the expression of the HPV oncogneic protein selected from the group consisting of HPV E7, HPV E6 and a combination thereof on the cancer cell in the mammal; and
wherein the antibody specific against the HPV oncogenic protein selected from the group consisting of HPV E7, HPV E6 and a combination thereof effects the death of the cancer cell expressing the HPV concogenic protein selected from the group consisting, of HPV E7, HPV E6 and a combination thereof in the mammal.
2. The method of claim 1 , wherein the immunogenic protein comprises at least one Major Histocompatihility Complex (MHC) class II epitope.
3. The method of claim 1 , wherein the elicited antibody triggers complement-dependent tumor cell lysis.
4. The method of claim 1 , wherein the stem cells and the vaccine composition are sequentially administered to the mammal.
5. The method of claim 1 , wherein the stem cells and the vaccine composition are concurrently administered, to the mammal.
6. The method of claim 1 , wherein the mesenchymal stem cells are derived from bone marrow or cord blood.
7. The method of claim 1 , wherein the cancer cell is at least one selected from the group consisting of a lung cancer cell and a sarcoma.
8. The method of claim 1 , wherein the mammal has metastatic cancer.
9. The method of claim 1 , wherein the immunogenic protein comprises it fusion protein comprising:
(a) a Psendomonas exotoxin A (PE) fragment comprising a binding domain and a translocation domain and without a cytotoxic domain;
(b) a human papillomavirus (HPV) Envelope protein selected from the group consisting of HPV E7, HPV E6, and a combination thereof; and
(c) a carboxyl terminal moiety comprising an endoplasmic retention sequence.