METHODS OF KILLING OR INHIBITING THE GROWTH OF CANCER CELLS
Provided herein, in certain embodiments, are compositions comprising an isolated heavy chain-hyaluronan/pentraxin 3 (“HC-HA/PTX3”) complex for use in methods of killing cancer cells. Also provided herein, are methods of inhibiting cancer cell regrowth of a tumor in an individual in need thereof, comprising contacting an area surrounding the tumor after a surgical procedure with an isolated HC-HA/PTX3 complex. Combinations and kits for use in practicing said methods also are provided herein.
1 . A method of inhibiting cancer cell regrowth of a tumor in an individual in need thereof, comprising contacting an area surrounding the tumor after a surgical procedure with an isolated heavy chain-hyaluronan/pentraxin 3 (HC-HA/PTX3) complex, thereby inhibiting cancer cell regrowth at the area surrounding the tumor.
2 . The method of claim 1 , wherein the surgical procedure comprises surgical excision, cryoablation, or radiofrequency ablation of the tumor.
3 . The method of claim 1 , wherein the surgical procedure comprises chemotherapy, immunotherapy, or targeted therapy.
4 . The method of claim 1 , wherein the area surrounding the tumor comprises a surgical margin.
5 . The method of claim 1 , wherein the area surrounding the tumor is a peritumor region.
6 . The method of claim 1 , wherein the tumor is a solid tumor.
7 . The method of claim 1 , wherein the tumor is a cancer selected from the group consisting of liver cancer, pancreatic cancer, bladder cancer, prostate cancer, lung cancer, non-small cell lung carcinoma, ovarian cancer, breast cancer, melanoma, gastric cancer, colon cancer, colorectal cancer, central nervous system (CNS) cancer, bone cancer, a lymphoma, skin cancer, head and neck cancer, kidney cancer, testicular cancer, uterine cancer, cervical cancer, esophageal cancer, thyroid cancer, salivary gland cancer, adrenal cancer, and gastrointestinal cancer.
8 . The method of claim 7 , wherein the cancer is an inoperable cancer.
9 . The method of claim 7 , wherein the cancer is pancreatic cancer.
10 . The method of claim 7 , wherein the cancer is prostate cancer.
11 . The method of claim 7 , wherein the cancer is glioblastoma multiforme.
12 . The method of claim 7 , wherein the cancer is skin cancer.
13 . The method of claim 7 , wherein the cancer is colon cancer.
14 . The method of claim 7 , wherein the cancer is lung cancer.
15 . The method of claim 7 , wherein the cancer is breast cancer.
16 . The method of claim 1 , wherein the area surrounding the tumor is contacted with about 10 microgram to 100 milligrams.
17 . The method of any one of claims 1 to 16 , wherein the HC-HA/PTX3 complex is native HC-HA/PTX3 complex, reconstituted HC-HA/PTX3 complex, or a combination thereof.
18 . The method of claim 17 , wherein the native HC-HA/PTX3 complex is isolated from a fetal support tissue.
19 . The method of claim 17 , wherein the reconstituted HC-HA/PTX3 complex comprises heavy chain 1 (HC1) and heavy chain 2 (HC2) of inter-α-inhibitor (IαI), hyaluronic acid (HA), and PTX3.
20 . The method of claim 17 , wherein the reconstituted HC-HA/PTX3 complex comprises HC1, HC2, HA, PTX3 and tumor necrosis factor α-stimulated gene 6 (TSG-6).
21 . The method of claim 1 , wherein the hyaluronan (HA) is high molecular weight hyaluronan (HMW HA).
22 . The method of claim 1 , wherein the hyaluronan (HA) is low molecular weight hyaluronan (LMW HA).
23 . The method of claim 1 , wherein the HC-HA/PTX3 complex is cryopreserved.
24 . The method of claim 1 , wherein the HC-HA/PTX3 complex comprises viable cells.
25 . The method of claim 1 , further comprising administering a therapeutic agent.
26 . The method of claim 25 , wherein the therapeutic agent is selected from the group consisting of a chemotherapeutic, an analgesic, an anti-inflammatory, a steroid, an immunotherapy, cellular therapy, a radiotherapy, a targeted drug therapeutic, and an antibiotic.
27 . The method of claim 25 , wherein administering the therapeutic agent occurs before contacting the area surrounding the tumor with the HC-HA/PTX3 complex.
28 . The method of claim 25 , wherein administering the therapeutic agent occurs after contacting the area surrounding the tumor with the HC-HA/PTX3 complex.
29 . The method of claim 25 , wherein administering the therapeutic agent occurs concurrently with contacting the area surrounding the tumor with the HC-HA/PTX3 complex.
30 . The method of any one of claims 1 to 29 , wherein the method inhibits tumor cell regrowth by killing cancer cells.
31 . The method of claim 30 , wherein the killing of the cancer cells is by apoptosis or necrosis.
32 . The method of any one of claims 1 to 29 , wherein the method inhibits tumor cell regrowth by inhibiting proliferation of cancer cells.
33 . The method of any one of claims 1 to 29 , wherein the method inhibits tumor cell regrowth by inhibiting metabolic activity of cancer cells.
34 . A method of killing cancer cells of a tumor in an individual in need thereof, comprising contacting a tumor or an area surrounding the tumor prior to, during or after a surgical procedure with an isolated heavy chain-hyaluronan/pentraxin 3 (HC-HA/PTX3) complex, thereby killing the cancer cells.
35 . The method of claim 34 , wherein the surgical procedure comprises surgical excision, cryoablation, or radiofrequency ablation of the tumor.
36 . The method of claim 34 , wherein the surgical procedure comprises chemotherapy, immunotherapy, or targeted therapy.
37 . The method of claim 34 , wherein the area surrounding the tumor comprises a surgical margin.
38 . The method of claim 34 , wherein the area surrounding the tumor is a peritumor region.
39 . The method of claim 34 , wherein the tumor is a solid tumor.
40 . The method of claim 34 , wherein the tumor is a cancer selected from the group consisting of liver cancer, pancreatic cancer, bladder cancer, prostate cancer, lung cancer, non-small cell lung carcinoma, ovarian cancer, breast cancer, melanoma, gastric cancer, colon cancer, colorectal cancer, central nervous system (CNS) cancer, bone cancer, a lymphoma, skin cancer, head and neck cancer, kidney cancer, testicular cancer, uterine cancer, cervical cancer, esophageal cancer, thyroid cancer, salivary gland cancer, adrenal cancer, and gastrointestinal cancer.
41 . The method of claim 34 , wherein the cancer is an inoperable cancer.
42 . The method of claim 34 , wherein the cancer is pancreatic cancer.
43 . The method of claim 34 , wherein the cancer is prostate cancer.
44 . The method of claim 34 , wherein the cancer is glioblastoma multiforme.
45 . The method of claim 34 , wherein the cancer is skin cancer.
46 . The method of claim 34 , wherein the cancer is colon cancer.
47 . The method of claim 34 , wherein the cancer is lung cancer.
48 . The method of claim 34 , wherein the cancer is breast cancer.
49 . The method of claim 34 , wherein the area surrounding the tumor is contacted with about 10 microgram to 100 milligrams.
50 . The method of any one of claims 34 to 49 , wherein the HC-HA/PTX3 complex is native HC-HA/PTX3 complex, reconstituted HC-HA/PTX3 complex, or a combination thereof.
51 . The method of claim 50 , wherein the native HC-HA/PTX3 complex is isolated from a fetal support tissue.
52 . The method of claim 50 , wherein the reconstituted HC-HA/PTX3 complex comprises heavy chain 1 (HC1) and heavy chain 2 (HC2) of inter-α-inhibitor (IαI), hyaluronic acid (HA), and PTX3.
53 . The method of claim 50 , wherein the reconstituted HC-HA/PTX3 complex comprises HC1, HC2, HA, PTX3 and tumor necrosis factor α-stimulated gene 6 (TSG-6).
54 . The method of claim 34 , wherein the HC-HA/PTX3 complex is cryopreserved.
55 . The method of claim 34 , wherein the HC-HA/PTX3 complex comprises viable cells.
56 . The method of claim 34 , wherein the hyaluronan (HA) is high molecular weight hyaluronan (HMW HA).
57 . The method of claim 34 , wherein the hyaluronan (HA) is low molecular weight hyaluronan (LMW HA).
58 . The method of claim 34 , wherein the contacting comprises injecting the HC-HA/PTX3 directly into a tumor.
59 . The method of claim 34 , further comprising administering a therapeutic agent.
60 . The method of claim 59 , wherein the therapeutic agent is selected from the group consisting of a chemotherapeutic, an analgesic, an anti-inflammatory, a steroid, an immunotherapy, cellular therapy, a radiotherapy, a targeted drug therapeutic, and an antibiotic.
61 . The method of claim 59 , wherein administering the therapeutic agent occurs before contacting the cancer cells with the HC-HA/PTX3 complex.
62 . The method of claim 59 , wherein administering the therapeutic agent occurs after contacting the cancer cells with the HC-HA/PTX3 complex.
63 . The method of claim 59 , wherein administering the therapeutic agent occurs concurrently with contacting the cancer cells with the HC-HA/PTX3 complex.
64 . The method of claim 34 , wherein the killing of the cancer cells is by apoptosis or necrosis.