CD29 targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of a pigmented melanoma model
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that utilizes an antibody-photoabsorber-conjugate (AbPC) combined with NIR light. The AbPC is injected and binds to the tumor whereupon NIR light irradiation causes a photochemical reaction that selectively kills cancer...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
|
| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2021.2019922 |
| _version_ | 1818754884482105344 |
|---|---|
| author | Aki Furusawa Ryuhei Okada Fuyuki Inagaki Hiroaki Wakiyama Takuya Kato Hideyuki Furumoto Hiroshi Fukushima Shuhei Okuyama Peter L. Choyke Hisataka Kobayashi |
| author_facet | Aki Furusawa Ryuhei Okada Fuyuki Inagaki Hiroaki Wakiyama Takuya Kato Hideyuki Furumoto Hiroshi Fukushima Shuhei Okuyama Peter L. Choyke Hisataka Kobayashi |
| author_sort | Aki Furusawa |
| collection | DOAJ |
| description | Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that utilizes an antibody-photoabsorber-conjugate (AbPC) combined with NIR light. The AbPC is injected and binds to the tumor whereupon NIR light irradiation causes a photochemical reaction that selectively kills cancer cells. NIR-PIT is ideal for surface-located skin cancers such as melanoma. However, there is concern that the pigment in melanoma lesions could interfere with light delivery, rendering treatment ineffective. We investigated the efficacy of CD29- and CD44-targeted NIR-PIT (CD29-PIT and CD44-PIT, respectively) in the B16 melanoma model, which is highly pigmented. While CD29-PIT and CD44-PIT killed B16 cells in vitro and in vivo, CD29-PIT suppressed tumor growth more efficiently. Ki67 expression showed that cells surviving CD29-PIT were less proliferative, suggesting that CD29-PIT was selective for more proliferative cancer cells. CD29-PIT did not kill immune cells, whereas CD44-PIT killed both T and NK cells and most myeloid cells, including DCs, which could interfere with the immune response to NIR-PIT. The addition of anti-CTLA4 antibody immune checkpoint inhibitor (ICI) to CD29-PIT increased the infiltration of CD8 T cells and enhanced tumor suppression with prolonged survival. Such effects were less prominent when the anti-CTLA4 ICI was combined with CD44-PIT. The preservation of immune cells in the tumor microenvironment (TME) after CD29-PIT likely led to a better response when combined with anti-CTLA4 treatment. We conclude that NIR-PIT can be performed in pigmented melanomas and that CD29 is a promising target for NIR-PIT, which is amenable to combination therapy with other immunotherapies. |
| first_indexed | 2024-12-18T05:30:21Z |
| format | Article |
| id | doaj.art-c84b464ade6a4b16a0279abd843ce507 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-18T05:30:21Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-c84b464ade6a4b16a0279abd843ce5072022-12-21T21:19:28ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2021.20199222019922CD29 targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of a pigmented melanoma modelAki Furusawa0Ryuhei Okada1Fuyuki Inagaki2Hiroaki Wakiyama3Takuya Kato4Hideyuki Furumoto5Hiroshi Fukushima6Shuhei Okuyama7Peter L. Choyke8Hisataka Kobayashi9National Cancer InstituteNational Cancer InstituteNational Cancer InstituteNational Cancer InstituteNational Cancer InstituteNational Cancer InstituteNational Cancer InstituteNational Cancer InstituteNational Cancer InstituteNational Cancer InstituteNear-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that utilizes an antibody-photoabsorber-conjugate (AbPC) combined with NIR light. The AbPC is injected and binds to the tumor whereupon NIR light irradiation causes a photochemical reaction that selectively kills cancer cells. NIR-PIT is ideal for surface-located skin cancers such as melanoma. However, there is concern that the pigment in melanoma lesions could interfere with light delivery, rendering treatment ineffective. We investigated the efficacy of CD29- and CD44-targeted NIR-PIT (CD29-PIT and CD44-PIT, respectively) in the B16 melanoma model, which is highly pigmented. While CD29-PIT and CD44-PIT killed B16 cells in vitro and in vivo, CD29-PIT suppressed tumor growth more efficiently. Ki67 expression showed that cells surviving CD29-PIT were less proliferative, suggesting that CD29-PIT was selective for more proliferative cancer cells. CD29-PIT did not kill immune cells, whereas CD44-PIT killed both T and NK cells and most myeloid cells, including DCs, which could interfere with the immune response to NIR-PIT. The addition of anti-CTLA4 antibody immune checkpoint inhibitor (ICI) to CD29-PIT increased the infiltration of CD8 T cells and enhanced tumor suppression with prolonged survival. Such effects were less prominent when the anti-CTLA4 ICI was combined with CD44-PIT. The preservation of immune cells in the tumor microenvironment (TME) after CD29-PIT likely led to a better response when combined with anti-CTLA4 treatment. We conclude that NIR-PIT can be performed in pigmented melanomas and that CD29 is a promising target for NIR-PIT, which is amenable to combination therapy with other immunotherapies.http://dx.doi.org/10.1080/2162402X.2021.2019922cancernear-infrared photoimmunotherapy (nir-pit)target moleculemelanomacd29 |
| spellingShingle | Aki Furusawa Ryuhei Okada Fuyuki Inagaki Hiroaki Wakiyama Takuya Kato Hideyuki Furumoto Hiroshi Fukushima Shuhei Okuyama Peter L. Choyke Hisataka Kobayashi CD29 targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of a pigmented melanoma model OncoImmunology cancer near-infrared photoimmunotherapy (nir-pit) target molecule melanoma cd29 |
| title | CD29 targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of a pigmented melanoma model |
| title_full | CD29 targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of a pigmented melanoma model |
| title_fullStr | CD29 targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of a pigmented melanoma model |
| title_full_unstemmed | CD29 targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of a pigmented melanoma model |
| title_short | CD29 targeted near-infrared photoimmunotherapy (NIR-PIT) in the treatment of a pigmented melanoma model |
| title_sort | cd29 targeted near infrared photoimmunotherapy nir pit in the treatment of a pigmented melanoma model |
| topic | cancer near-infrared photoimmunotherapy (nir-pit) target molecule melanoma cd29 |
| url | http://dx.doi.org/10.1080/2162402X.2021.2019922 |
| work_keys_str_mv | AT akifurusawa cd29targetednearinfraredphotoimmunotherapynirpitinthetreatmentofapigmentedmelanomamodel AT ryuheiokada cd29targetednearinfraredphotoimmunotherapynirpitinthetreatmentofapigmentedmelanomamodel AT fuyukiinagaki cd29targetednearinfraredphotoimmunotherapynirpitinthetreatmentofapigmentedmelanomamodel AT hiroakiwakiyama cd29targetednearinfraredphotoimmunotherapynirpitinthetreatmentofapigmentedmelanomamodel AT takuyakato cd29targetednearinfraredphotoimmunotherapynirpitinthetreatmentofapigmentedmelanomamodel AT hideyukifurumoto cd29targetednearinfraredphotoimmunotherapynirpitinthetreatmentofapigmentedmelanomamodel AT hiroshifukushima cd29targetednearinfraredphotoimmunotherapynirpitinthetreatmentofapigmentedmelanomamodel AT shuheiokuyama cd29targetednearinfraredphotoimmunotherapynirpitinthetreatmentofapigmentedmelanomamodel AT peterlchoyke cd29targetednearinfraredphotoimmunotherapynirpitinthetreatmentofapigmentedmelanomamodel AT hisatakakobayashi cd29targetednearinfraredphotoimmunotherapynirpitinthetreatmentofapigmentedmelanomamodel |