Advances in Cancer Drug Targets

Volume: 1

Anticancer Immunotherapy in Combination with Proapoptotic Therapy - Possible Therapeutic Strategies for Enhancement of Anticancer Immune Reactivity in Autologous Immunocompetent Cells and After Allogeneic Stem Cell Transplantation

Author(s): Håkon Reikvam, Elisabeth Ersvær, Guro Kristin Melve, Astrid Olsnes Kittang, Bjørn Tore Gjertsen and Øystein Bruserud

Pp: 172-206 (35)

DOI: 10.2174/9781608054749113010008

* (Excluding Mailing and Handling)

Abstract

Induction of immune responses against cancer-associated antigens is possible, but the optimal use of this strategy remains to be established and especially the combination of T cell therapy and new targeted therapeutic agents should be investigated. The design of future clinical studies has to consider several issues. Firstly, induction of anticancer T cell reactivity seems most effective in patients with low disease burden. Initial disease-reducing therapy including surgery, irradiation and conventional or new targeted chemotherapy should therefore be used, preferably through induction of immunogenic cancer cell death. Secondly, after the induction phase effector T cells will induce cancer cell apoptosis mainly through the intrinsic apoptosis-regulating pathway. The effect of this effector T cell function should be strengthened by administration of chemotherapy that mediates additional proapoptotic signalling through the external apoptosis-regulating pathway, inhibition of survival signalling or blocking of anti-apoptotic signalling. Thirdly, the status of the immune system has to be considered, including the postchemotherapy CD4+ T cell defect, the balance between proinflammatory and immunosuppressive T cell subsets (e.g. regulatory T cells versus Th17 cells), and immunoregulatory mesenchymal cells that can be detected within tumors. Immunotherapy should probably be initiated early after disease-reducing therapy when the cancer cell burden is lowest and a focus should then be to alter the balance in favour of proinflammatory T cell subsets. All these issues need to be considered in the design of future clinical studies combining chemotherapy and immunotherapy.


Keywords: Cancer, T cells, Apoptosis, Immunotherapy, Chemotherapy, Allogeneic stem cell transplantation.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873443466 and j.to_ip >=873443466 )) and ((j.from_date <= 1739835008 and j.to_date >= 1739835008 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4784) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873443466 and j.to_ip >=873443466 )) and ((j.from_date <= 1739835008 and j.to_date >= 1739835008 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4784) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 873443466 and j.to_ip >=873443466 )) and ((j.from_date <= 1739835008 and j.to_date >= 1739835008 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 4784)
      900μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1176 and `b`.`banner_from_date` <= 1739835008 and `b`.`banner_to_date` >= 1739835008 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.21msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1176
      • 3: 1739835008
      • 4: 1739835008
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='52d1fc73d8b73e9adc329ade1557beef'
      320μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    6Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        tFP8Fvx8Vnwum5EHKQuKCntkEWTXck3zxgCvWOCL
        uc_cart_id
        52d1fc73d8b73e9adc329ade1557beef
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/4784" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/4784
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        0 of 0
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        response_headers
        0 of 0
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        array:5 [ "_token" => "tFP8Fvx8Vnwum5EHKQuKCntkEWTXck3zxgCvWOCL" "uc_cart_id" => "52d1fc73d8b73e9adc329ade1557beef" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/4784" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:30:08GET/chapter/4784112198