Invented by Andrea MAHR, Toni Weinschenk, Colette SONG, Oliver Schoor, Jens FRITSCHE, Harpreet Singh, Immatics Biotechnologies GmbH

The market for peptides, peptide combinations, and immunotherapy for various cancers has seen significant growth in recent years. This review aims to provide an overview of the current market landscape, highlighting key players, advancements, challenges, and future prospects in this field. Peptides are short chains of amino acids that play crucial roles in various biological processes. They have gained attention in cancer research due to their ability to selectively target cancer cells, leading to more effective and less toxic treatments. Peptide-based therapies have shown promise in treating a wide range of cancers, including breast, lung, prostate, and melanoma. One of the key drivers of the market for peptides and peptide combinations is the increasing prevalence of cancer worldwide. According to the World Health Organization (WHO), cancer is one of the leading causes of death globally, with approximately 9.6 million deaths in 2018. This rising burden has prompted researchers and pharmaceutical companies to explore novel treatment options, including peptides and peptide combinations. Immunotherapy, on the other hand, harnesses the body’s immune system to fight cancer cells. It has emerged as a groundbreaking approach in cancer treatment, with several immunotherapeutic agents receiving regulatory approval in recent years. Peptide-based immunotherapy, such as cancer vaccines and immune checkpoint inhibitors, has shown remarkable efficacy in certain cancer types, leading to increased investment and research in this area. The market for peptides, peptide combinations, and immunotherapy is highly competitive, with several major players dominating the landscape. Pharmaceutical giants like Merck & Co., Bristol-Myers Squibb, and Roche have made significant investments in developing and commercializing peptide-based therapies. These companies have successfully launched products such as Keytruda, Opdivo, and Tecentriq, which have revolutionized cancer treatment and generated substantial revenues. Advancements in peptide synthesis and manufacturing technologies have also contributed to the growth of this market. The development of solid-phase peptide synthesis (SPPS) and recombinant DNA technology has enabled the production of large quantities of high-quality peptides at a lower cost. This has facilitated the development of peptide-based therapies and expanded their accessibility to a larger patient population. Despite the progress made, there are still challenges to overcome in the market for peptides and immunotherapy. One major hurdle is the high cost associated with peptide-based therapies, which limits their affordability and accessibility. Additionally, the complex nature of cancer and the heterogeneity of tumors pose challenges in developing effective peptide combinations that can target multiple cancer types. Looking ahead, the future of the market for peptides, peptide combinations, and immunotherapy appears promising. The increasing understanding of cancer biology and the advent of precision medicine are expected to drive the development of personalized peptide-based therapies. Moreover, ongoing research in areas such as neoantigens, tumor microenvironment, and combination therapies holds great potential for further advancements in cancer treatment. In conclusion, the market for peptides, peptide combinations, and immunotherapy for various cancers is witnessing significant growth and innovation. With the rising prevalence of cancer and the increasing demand for effective and targeted therapies, the development and commercialization of peptide-based treatments are expected to continue expanding. However, addressing challenges related to cost, tumor heterogeneity, and accessibility will be crucial in realizing the full potential of these therapies in improving patient outcomes.

The Immatics Biotechnologies GmbH invention works as follows

The invention concerns peptides and proteins as well as cells that can be used in immunotherapeutic procedures. The present invention is particularly relevant to immunotherapy for cancer. The invention also relates to tumor-associated T cell peptide epitopes. These can be used alone or in combination, to stimulate immune responses or T cells ex-vivo for transplantation into patients. Antibodies, soluble T cell receptors and other binding molecules can target peptides bound to the major histocompatibility complicated (MHC) or peptides in general.

Background for Peptides, peptide combinations and immunotherapy for various cancers: a review

According to the World Health Organization, cancer was one of the top four non-communicable diseases in the world in 2012. In the same year, colorectal, breast and respiratory cancers were among the top 10 causes for death in high-income countries.


In 2012, worldwide, it was estimated that 14.1 million new cases of cancer, 32.6 millions cancer patients (within five years of diagnosis), and 8.2million cancer deaths occurred (Ferlay, Bray, et. al., 2013, 2013). Tables 1 and 2 give an overview of estimated incidence, 5-year prevalence, and mortality for different cancer types relevant to the current intervention worldwide and in selected areas, respectively.

TABLE 1\nEstimated incidence, 5 year prevalence and mortality of different\ncancer types (adult population, both sexes) worldwide in 2012\n(Ferlay et al., 2013; Bray et al., 2013).\nPrevalence\nCancer Incidence (5 year) Mortality\nBrain, nervous system 256213 342914 189382\nBreast 1671149 6232108 521907\nColorectum 1360602 3543582 693933\nEsophagus 455784 464063 400169\nKidney 337860 906746 143406\nLeukemia 351965 500934 265471\nLiver 782451 633170 745533\nLung 1824701 1893078 1589925\nMelanoma 232130 869754 55488\nOvary 238719 586624 151917\nPancreas 337872 211544 330391\nProstate 1094916 3857500 307481\nStomach 951594 1538127 723073\nGallbladder 178101 205646 142823\nBladder 429793 1319749 165084\nCorpus uteri 319605 1216504 76160\nNon-Hodgkin lymphoma 385741 832843 199670

TABLE 2\nEstimated incidence, 5 year prevalence and mortality of different\ncancer types (adult population, both sexes) in the USA, EU-28,\nChina and Japan in 2012 (Ferlay et al., 2013; Bray et al., 2013).\nPrevalence\nCancer Incidence (5 year) Mortality\nBrain, nervous system 135884 172497 100865\nBreast 837245 3358034 197279\nColorectum 845797 2334303 396066\nEsophagus 294734 323723 255752\nKidney 226733 631350 83741\nLeukemia 178296 309154 129500\nLiver 513172 441007 488485\nLung 1274568 1394735 1107546\nMelanoma 163043 636364 32999\nOvary 108947 270204 65130\nPancreas 220842 134864 214886\nProstate 681069 2586710 136419\nStomach 615641 1076332 447735\nGallbladder 106202 118588 81391\nBladder 270335 879140 91553\nCorpus uteri 199211 765101 41734\nNon-Hodgkin lymphoma 205955 515154 90092

The current invention focuses specifically on glioblastoma, chronic lymphocytic (CLL), acute myeloid (AML), and non-small and small cell lung carcinoma (NSCLC) respectively.

The United States has the highest incidence of GB, with an age-adjusted rate of 3,19 per 100,000 residents. GB is a disease with a poor prognosis. It has a survival rate for the first year of only 35%, and a survival rate for five years that is less than 5%. “The risk factors of GB are male gender, older age, and ethnicity (Thakkar et. al.,2014).

CLL is the most common form of leukemia in Western countries, where it accounts for about one-third of all leukemia. The incidence rates in the US are comparable to those in Europe. New cases are estimated at 16,000 each year. CLL is commoner in Caucasians compared to Africans. It’s rarer among Hispanics, Native Americans, and Asians. CLL rates in people of Asian descent are three times lower than those in Caucasians. (Gunawardana, et. al., 2008). Patients with CLL have a five-year survival rate of 79%.

AML is the second-most common leukemia in adults and children. About 21,000 new cases are estimated to occur in the United States each year. “The five-year survival rates of AML patients are approximately 25%.

Lung cancer is the second most common cancer type in the world and the number one cause of cancer-related death in many countries. Lung cancer can be divided into non-small and small cell lung carcinoma. NSCLC is comprised of the histological types large cell carcinoma, squamous-cell carcinoma and adenocarcinoma. It accounts for 85% all lung cancers diagnosed in the United States. The incidence of NSCLC, which includes current and former smokers, is closely related to smoking prevalence.


Breast Cancer

Breast cancer is immunogenic and the different types of immune cells that infiltrate primary tumors have distinct prognostic or predictive significance. Breast cancer patients have undergone a large number of immunotherapy early phase trials. The majority of completed vaccination studies focused on HER2 and carbohydrates antigens such as MUC-1, and showed disappointing results. “Emens (2012)” reports that clinical data are now emerging on the effect of immune checkpoint moderating with ipilimumab or other T-cell activating antibodies against breast cancer.

Chronic Leukemia

While CLL is currently incurable, some patients only show a slow progression or worsening symptoms. Since early treatment is not beneficial to patients, the first approach should be ‘watch and wait’. (Richards et al., 1999). There are several treatment options available for patients with symptoms or disease that is rapidly progressing. They include chemotherapy, immune-based treatments like monoclonal antibody, chimeric Antigen-Receptors (CARs), active immunotherapy and stem cell transplants.

Monoclonal antibody is widely used for hematologic cancers.” It is because of the availability of tumor cells and blood in bone marrow or the ability to identify suitable antigens. Monoclonal antibodies commonly used in CLL treatment target CD20 or CD52. Rituximab is the first monoclonal antibody against CD20 that was approved by FDA to treat NHLs. It is now widely used for CLL treatment. Combinational treatment with rituximab/fludarabine/cyclophosphamide leads to higher CR rates and improved overall survival (OS) compared to the combination fludarabine/cyclophosphamide and has become the preferred treatment option (Hallek et al., 2008). Ofatumomab is a CD20-targeting antibody used to treat refractory CLL (Wierda and al., 2011). Obinutuzumab, a monoclonal anti CD20 antibody is used as a first-line treatment with chlorambucil.

Alemtuzumab is an anti-CD52 antibody used for treatment of patients with chemotherapy-resistant disease or patients with poor prognostic factors as del 17p or p53 mutations (Parikh et al., 2011). Novel monoclonal antibody targets CD37 (otlertuzumab), CD40 (dacetuzumab), or CD37 (177) Lu-tetulomab (BI 836826, IMGN529, and (177) Lu -tetulomab. These antibodies are tested pre-clinically (Robak & Robak, 2014).

Several ongoing and completed trials are based upon engineered autologous CAR-modified T cell with CD19 specificity” (Maus et. al.,2014). Only a minority of patients have shown detectable CARs or persistent CARs. Porter et al. have detected two complete responses and one partial response in CAR T cell trials. and Kalos et al. (Kalos et al., 2011; Porter et al., 2011).

Active Immunotherapy includes strategies such as gene therapy, whole modified tumour cell vaccines (WMCV), DC-based vaccines, and tumor-associated antigen-derived peptides.

Gene therapy approaches use autologous genetically altered tumor cells. These B-CLL cells are transfected with immuno-(co-)stimulatory genes like IL-2, IL-12, TNF-alpha, GM-CSF, CD80, CD40L, LFA-3 and ICAM-1 to improve antigen presentation and T cell activation (Carballido et al., 2012). “While specific T-cell response and reduction of tumor cells can be observed, immune responses only last a short time.

Several studies have used autologous DCs to present antigens and elicit antitumor responses. Ex vivo, DCs were loaded with tumor-associated peptides or whole tumor cell lysate. They also received tumor-derived DNA or RNA. One strategy involves fusion of whole tumor cells with DCs to generate DC-B-CLL hybrids. Transfected DCs induced both CD4+and CD8+T-cell responses. (Muller and al., 2004). Fusion hybrids, DCs loaded up with tumor cell lysate and apoptotic body induced tumor-specific CD8+T-cell responses. Patients who showed a clinical reaction had higher IL-12 levels in their serum and fewer Tregs.

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